المؤلفون: Neven, P., Fasching, P. A., Chia, S., Jerusalem, G., De Laurentiis, M., Im, S. A., Cruz Merino, Luis de la, Slamon, D. J.

المساهمون: Universidad de Sevilla. Departamento de Medicina, Universidad de Sevilla. CTS151: Bioquímica médica.

مصطلحات موضوعية: Ribociclib, CDK4/6 inhibitor, Advanced breast cancer, Overall survival, First line

الوصف: Background The phase III MONALEESA-3 trial included frst- (1L) and second-line (2L) patients and demonstrated a signifcant overall survival (OS) beneft for ribociclib+fulvestrant in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−) advanced breast cancer (ABC) in the fnal protocol-specifed and exploratory (longer follow-up) OS analyses. At the time of these analyses, the full OS beneft of 1L ribociclib was not completely characterized because the median OS (mOS) was not reached. As CDK4/6 inhibi‑ tor (CDK4/6i)+endocrine therapy (ET) is now a preferred option for 1L HR+/HER2− ABC, we report an exploratory analysis (median follow-up, 70.8 months; 14.5 months longer than the prior analysis) to fully elucidate the OS beneft in the MONALEESA-3 1L population. Methods Postmenopausal patients with HR+/HER2− ABC were randomized 2:1 to 1L/2L fulvestrant+riboci‑ clib or placebo. OS in 1L patients (de novo disease or relapse>12 months from completion of [neo]adjuvant ET) was assessed by Cox proportional hazards model and Kaplan–Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were analyzed. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615). Results At data cutof (January 12, 2022; median follow-up time, 70.8 months), mOS was 67.6 versus 51.8 months with 1L ribociclib versus placebo (hazard ratio (HR) 0.67; 95% CI 0.50–0.90); 16.5% and 8.6% of ribociclib and placebo patients, respectively, were still receiving treatment. PFS2 (HR 0.64) and CFS (HR 0.62) favored ribociclib versus pla‑ cebo. Among those who discontinued treatment, 16.7% and 35.0% on ribociclib or placebo, respectively, received a subsequent CDK4/6i. No new safety signals were observed. This analysis of MONALEESA-3 reports the longest mOS thus far (67.6 months) for 1L patients in a phase III ABC trial. These results in a 1L population show that the OS beneft of ribociclib was maintained through extended follow-up, further supporting its use in HR+/HER2− ...

العلاقة: Breast Cancer Research, 25 (1), 103.; https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-023-01701-9Test; https://idus.us.es/handle//11441/155798Test

الإتاحة: https://idus.us.es/handle//11441/155798Test

المؤلفون: Туксаитова Райхан Омерзаковна, НАО «Казахский агротехнический исследовательский университет им. С. Сейфуллина», Raikhan O. Tuksaitova, Kazakhskii agrotekhnicheskii universitet im. S. Seifullina, Омарова Гульнар Турсуновна, Gulnar T. Omarova, Альбекова Асия Шакеновна, Asiia S. Al'bekova, Кукенова Гульжихан Ануарбековна, Gul'zhikhan A. Kukenova

المصدر: Education, innovation, research as a resource for community development; 267-269 ; Образование, инновации, исследования как ресурс развития сообщества; 267-269

مصطلحات موضوعية: коммуникативная компетенция, профессиональная лексика, информационно-коммуникативные технологии, комплексный анализ текста

الوصف: В статье рассматривается вопрос об использовании на занятиях русского языка комплексного анализа текста с целью актуализации и мотивации знаний, формирования умений и навыков на основе применения полученных знаний, рефлексии. При этом преподаватель имеет возможность в течение учебного занятия менять формы работы: групповая, индивидуальная, работа в парах, в подгруппах.

وصف الملف: text/html

العلاقة: info:eu-repo/semantics/altIdentifier/isbn/978-5-907830-01-1; https://phsreda.com/e-articles/10572/Action10572-109212.pdfTest; Романова Т.В. Анализ текста как средство развития речи учащихся / Т.В. Романова // Русский язык в школе. – 1989. – №1.; Сергеев И.С. Как реализовать компетентностный подход на уроке и во внеурочной деятельности: практическое пособие / И.С. Сергеев, В.И. Блинов. – М.: АРКТИ, 2007. – EDN QVQJKH; Быстрова Е.А. Коммуникативная методика в преподавании родного языка / Е.А. Быстрова // РЯШ. – 1996. – №1.; https://phsreda.com/files/Books/10572/Cover-10572.jpg?req=109212Test; https://phsreda.com/article/109212/discussion_platformTest

الإتاحة: https://phsreda.com/article/109212/discussion_platformTest
https://phsreda.com/files/Books/10572/Cover-10572.jpg?req=109212Test

المؤلفون: Drew, Y, Kim, J-W, Penson, RT, O'Malley, DM, Parkinson, C, Roxburgh, P, Plummer, R, Im, S-A, Imbimbo, M, Ferguson, M, Rosengarten, O, Steeghs, N, Kim, MH, Gal-Yam, E, Tsoref, D, Kim, J-H, You, B, De Jonge, M, Lalisang, R, Gort, E, Bastian, S, Meyer, K, Feeney, L, Baker, N, Ah-See, M-L, Domchek, SM, Banerjee, S, MEDIOLA Investigators

المساهمون: Banerjee, Susana

مصطلحات موضوعية: Humans, Female, Bevacizumab, Poly(ADP-ribose) Polymerase Inhibitors, Ovarian Neoplasms, Cohort Studies, Germ-Line Mutation, Antineoplastic Agents, Phthalazines, Carcinoma, Ovarian Epithelial, Neoplasm Recurrence, Local

جغرافية الموضوع: United States

الوصف: PURPOSE: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts). PATIENTS AND METHODS: In this open-label, multicenter study, PARP inhibitor-naïve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab. Primary endpoints were objective response rate (ORR; gBRCAm expansion doublet cohort), disease control rate (DCR) at 24 weeks (non-gBRCAm cohorts), and safety (all cohorts). RESULTS: The full analysis and safety analysis sets comprised 51, 32, and 31 patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively. ORR was 92.2% [95% confidence interval (CI), 81.1-97.8] in the gBRCAm expansion doublet cohort (primary endpoint); DCR at 24 weeks was 28.1% (90% CI, 15.5-43.9) in the non-gBRCAm doublet cohort (primary endpoint) and 74.2% (90% CI, 58.2-86.5) in the non-gBRCAm triplet cohort (primary endpoint). Grade ≥ 3 adverse events were reported in 47.1%, 65.6%, and 61.3% of patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively, most commonly anemia. CONCLUSIONS: Olaparib plus durvalumab continued to show notable clinical activity in women with gBRCAm PSROC. Olaparib plus durvalumab with bevacizumab demonstrated encouraging clinical activity in women with non-gBRCAm PSROC. No new safety signals were identified.

وصف الملف: Print; 62; application/pdf

العلاقة: 730052; Clinical Cancer Research, 2024, 30 (1), pp. 50 - 62; https://repository.icr.ac.uk/handle/internal/6148Test

الإتاحة: https://doi.org/10.1158/1078-0432.CCR-23-2249Test
https://repository.icr.ac.uk/handle/internal/6148Test

المؤلفون: Park, K.H., Loibl, S., Sohn, J., Park, Y.H., Jiang, Z., Tadjoedin, H., Nag, S., Saji, S., Md. Yusof, M., Villegas, E.M.B., Lim, E.H., Lu, Y.-S., Ithimakin, S., Tseng, L.-M., Dejthevaporn, T., Chen, T.W.-W., Lee, S.C., Galvez, C., Malwinder, S., Kogawa, T., Bajpai, J., Brahma, B., Wang, S., Curigliano, G., Yoshino, T., Kim, S.-B., Pentheroudakis, G., Im, S.-A., Andre, F., Ahn, J.B., Harbeck, N.

المصدر: ESMO Open ; page 102974 ; ISSN 2059-7029

مصطلحات موضوعية: Cancer Research, Oncology

الإتاحة: https://doi.org/10.1016/j.esmoop.2024.102974Test
https://api.elsevier.com/content/article/PII:S2059702924007427?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2059702924007427?httpAccept=text/plainTest

المؤلفون: Yoon, Y.S., Amare, Y., Angelaszek, D., Anthony, N., Cheryian, K., Choi, G.H., Copley, M., Coutu, S., Derome, L., Eraud, L., Hagenau, L., Han, J.H., Huh, H.G., Hwang, Y.S., Hyun, H.J., Im, S., Jeon, H.B., Jeon, J.A., Jeong, S., Kang, S.C., Kim, H.J., Kim, K.C., Kim, M.H., Lee, H.Y., Lee, J., Lee, M.H., Liang, J., Lu, L., Lutz, L., Menchaca-Rocha, A., Mitchell, J.W., Mognet, S.I., Morton, S., Nester, M., Nutter, S., Park, H., Park, I.H., Park, J.M., Picot-Clémente, N., Seo, E.S., Smith, J.R., Walpole, P., Weinmann, R.P., Wu, J., Zhang, H.G.

المساهمون: NASA, National Autonomous University of Mexico Institute of Ecology, Korea Ministry of Science and ICT

المصدر: Astroparticle Physics ; volume 158, page 102947 ; ISSN 0927-6505

مصطلحات موضوعية: Astronomy and Astrophysics

الإتاحة: https://doi.org/10.1016/j.astropartphys.2024.102947Test
https://api.elsevier.com/content/article/PII:S0927650524000240?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0927650524000240?httpAccept=text/plainTest

المؤلفون: Dent, R., André, F., Gonçalves, A., Martin, M., Schmid, P., Schütz, F., Kümmel, S., Swain, S.M., Bilici, Ahmet, Loirat, D., Villalobos, Valencia R., Im, S. A., Park, Y. H., De Laurentis, M., Colleoni, M., Guarneri, V., Bianchini, G., Li, H., Kirchmayer Machackova, Z., Mouta, J., Deurloo, R., Gan, X., Fan, M., Mani, A., Swat, A., Cortés, J.

مصطلحات موضوعية: Disease-Free Interval, Immune Checkpoint, PD-L1, Prognosis, Rapid Relapse, Triple-Negative Breast Cancer

الوصف: Background: Immune checkpoint inhibitors improve the efficacy of first-line chemotherapy for patients with programmed death-ligand 1 (PD-L1)-positive unresectable locally advanced/metastatic triple-negative breast cancer (aTNBC), but randomised data in rapidly relapsing aTNBC are scarce. Patients and methods: IMpassion132 (NCT03371017) enrolled patients with aTNBC relapsing <12 months after last chemotherapy dose (anthracycline and taxane required) or surgery for early TNBC. PD-L1 status was centrally assessed using SP142 before randomisation. Initially patients were enrolled irrespective of PD-L1 status. From August 2019, enrolment was restricted to PD-L1-positive (tumour immune cell ≥1%) aTNBC. Patients were randomised 1:1 to placebo or atezolizumab 1200 mg every 21 days with investigator-selected chemotherapy until disease progression or unacceptable toxicity. Stratification factors were chemotherapy regimen (carboplatin plus gemcitabine or capecitabine monotherapy), visceral (lung and/or liver) metastases and (initially) PD-L1 status. The primary endpoint was overall survival (OS), tested hierarchically in patients with PD-L1-positive tumours and then, if positive, in the modified intent-to-treat (mITT) population (all-comer patients randomised pre-August 2019). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. Results: Among 354 patients with rapidly relapsing PD-L1-positive aTNBC, 68% had a disease-free interval of <6 months and 73% received carboplatin/gemcitabine. The OS hazard ratio was 0.93 (95% confidence interval 0.73-1.20, P = 0.59; median 11.2 months with placebo versus 12.1 months with atezolizumab). mITT and subgroup results were consistent. Median PFS was 4 months across treatment arms and populations. ORRs were 28% with placebo versus 40% with atezolizumab. Adverse events (predominantly haematological) were similar between arms and as expected with atezolizumab plus carboplatin/gemcitabine or capecitabine following recent chemotherapy ...

وصف الملف: application/pdf

العلاقة: Annals of Oncology; Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı; Dent, R., André, F., Gonçalves, A., Martin, M., Schmid, P., Schütz, F. . Cortés, J. (2024). IMpassion132 double-blind randomised phase III trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer. Annals of Oncology, 35(7), 630-642. http://dx.doi.org/10.1016/j.annonc.2024.04.001Test; http://dx.doi.org/10.1016/j.annonc.2024.04.001Test; https://hdl.handle.net/20.500.12511/12688Test; 35; 630; 642; 2-s2.0-85194586344; Q1

الإتاحة: https://doi.org/20.500.12511/1268810.1016/j.annonc.2024.04.001Test
https://hdl.handle.net/20.500.12511/12688Test

المؤلفون: Jeon JH, Im S, Kim HS, Lee D, Jeong K, Ku JM, Nam TG

المصدر: Drug Design, Development and Therapy, Vol Volume 16, Pp 4385-4397 (2022)

مصطلحات موضوعية: endoplasmic reticulum stress, unfolded protein response, chemical chaperone, drug discovery, diabetes, cardiovascular disease, neurodegeneration, lysosomal storage disease, Therapeutics. Pharmacology, RM1-950

الوصف: Jae-Ho Jeon,1,* Somyoung Im,1,* Hyo Shin Kim,1 Dongyun Lee,1 Kwiwan Jeong,2 Jin-Mo Ku,2 Tae-Gyu Nam1 1Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University ERICA campus, Ansan, Gyeonggi-do, 15588, Republic of Korea; 2Gyeonggi Bio-Center, Gyeonggido Business and Science Accelerator, Suwon, Gyeonggi-do, 16229, Republic of Korea*These authors contributed equally to this workCorrespondence: Tae-Gyu Nam, Tel +82-31-400-5807, Fax +82-31-400-5958, Email tnam@hanyang.ac.krAbstract: The endoplasmic reticulum (ER) is responsible for structural transformation or folding of de novo proteins for transport to the Golgi. When the folding capacity of the ER is exceeded or excessive accumulation of misfolded proteins occurs, the ER enters a stressed condition (ER stress) and unfolded protein responses (UPR) are triggered in order to rescue cells from the stress. Recovery of ER proceeds toward either survival or cell apoptosis. ER stress is implicated in many pathologies, such as diabetes, cardiovascular diseases, inflammatory diseases, neurodegeneration, and lysosomal storage diseases. As a survival or adaptation mechanism, chaperone molecules are upregulated to manage ER stress. Chemical versions of chaperone have been developed in search of drug candidates for ER stress-related diseases. In this review, synthetic or semi-synthetic chemical chaperones are categorized according to potential therapeutic area and listed along with their chemical structure and activity. Although only a few chemical chaperones have been approved as pharmaceutical drugs, a dramatic increase in literatures over the recent decades indicates enormous amount of efforts paid by many researchers. The efforts warrant clearer understanding of ER stress and the related diseases and consequently will offer a promising drug discovery platform with chaperone activity.Keywords: endoplasmic reticulum stress, unfolded protein response, chemical chaperone, drug discovery, diabetes, cardiovascular disease, neurodegeneration, lysosomal storage disease

وصف الملف: electronic resource

العلاقة: https://www.dovepress.com/chemical-chaperones-to-inhibit-endoplasmic-reticulum-stress-implicatio-peer-reviewed-fulltext-article-DDDTTest; https://doaj.org/toc/1177-8881Test

الوصول الحر: https://doaj.org/article/16a4daf3ac8e4fb89e823f247a26d6f1Test

المؤلفون: Neven, P., Fasching, P.A., Chia, S., Jerusalem, G., De, Laurentiis M., Im, S.-A., Petrakova, K., Bianchi, G.V., Martin, M., Nusch, A., Sonke, G.S., De, la Cruz-Merino L., Beck, J.T., Zarate, J.P., Wang, Y., Chakravartty, A., Wang, C., Slamon, D.J.

المساهمون: Im, S.-A.

مصطلحات موضوعية: ABEMACICLIB PLUS, PATIENTS PTS, PALBOCICLIB, THERAPY, LETROZOLE, INTERIM, Advanced breast cancer, CDK4/6 inhibitor, First line, Overall survival, Ribociclib

الوصف: Background: The phase III MONALEESA-3 trial included first- (1L) and second-line (2L) patients and demonstrated a significant overall survival (OS) benefit for ribociclib + fulvestrant in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−) advanced breast cancer (ABC) in the final protocol-specified and exploratory (longer follow-up) OS analyses. At the time of these analyses, the full OS benefit of 1L ribociclib was not completely characterized because the median OS (mOS) was not reached. As CDK4/6 inhibitor (CDK4/6i) + endocrine therapy (ET) is now a preferred option for 1L HR+/HER2− ABC, we report an exploratory analysis (median follow-up, 70.8 months; 14.5 months longer than the prior analysis) to fully elucidate the OS benefit in the MONALEESA-3 1L population. Methods: Postmenopausal patients with HR+/HER2− ABC were randomized 2:1 to 1L/2L fulvestrant + ribociclib or placebo. OS in 1L patients (de novo disease or relapse > 12 months from completion of [neo]adjuvant ET) was assessed by Cox proportional hazards model and Kaplan–Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were analyzed. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615). Results: At data cutoff (January 12, 2022; median follow-up time, 70.8 months), mOS was 67.6 versus 51.8 months with 1L ribociclib versus placebo (hazard ratio (HR) 0.67; 95% CI 0.50–0.90); 16.5% and 8.6% of ribociclib and placebo patients, respectively, were still receiving treatment. PFS2 (HR 0.64) and CFS (HR 0.62) favored ribociclib versus placebo. Among those who discontinued treatment, 16.7% and 35.0% on ribociclib or placebo, respectively, received a subsequent CDK4/6i. No new safety signals were observed. Conclusions: This analysis of MONALEESA-3 reports the longest mOS thus far (67.6 months) for 1L patients in a phase III ABC trial. These results in a 1L population show that the OS benefit of ribociclib was maintained through extended follow-up, further ...

العلاقة: Breast Cancer Research, Vol.25 No.1, p. 103; https://hdl.handle.net/10371/195837Test; 001055913300001; 2-s2.0-85169355504; 192406

الإتاحة: https://doi.org/10.1186/s13058-023-01701-9Test
https://hdl.handle.net/10371/195837Test

المؤلفون: Im, S.-A., Gennari, A., Park, Y.H., Kim, J.H., Jiang, Z.-F., Gupta, S., Fadjari, T.H., Tamura, K., Mastura, M.Y., Abesamis-Tiambeng, M.L.T., Lim, E.H., Lin, C.-H., Sookprasert, A., Parinyanitikul, N., Tseng, L.-M., Lee, S.-C., Caguioa, P., Singh, M., Naito, Y., Hukom, R.A., Smruti, B.K., Wang, S.-S., Kim, S.B., Lee, K.-H., Ahn, H.K., Peters, S., Kim, T.W., Yoshino, T., Pentheroudakis, G., Curigliano, G., Harbeck, N.

المساهمون: Im, S.-A.

مصطلحات موضوعية: ALPELISIB PLUS FULVESTRANT, PHASE-III TRIAL, DOUBLE-BLIND, SACITUZUMAB GOVITECAN, OPEN-LABEL, 1ST-LINE THERAPY, TRASTUZUMAB DERUXTECAN, REPORTED OUTCOMES, BRAIN METASTASIS, FINAL ANALYSIS, ESMO, guidelines, metastatic breast cancer, Pan-Asian, treatment

الوصف: The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies. ; Y ; 1

العلاقة: Esmo Open, Vol.8 No.3, p. 101541; https://hdl.handle.net/10371/194677Test; 001044740800001; 2-s2.0-85159041839; 185406

الإتاحة: https://doi.org/10.1016/j.esmoop.2023.101541Test
https://hdl.handle.net/10371/194677Test

المؤلفون: Tutt, A. N. J., Garber, J., Gelber, R. D., Phillips, K-A, Eisen, A., Johannsson, O. T., Rastogi, P., Cui, K. Y., Im, S-A, Yerushalmi, R., Brufsky, A. M., Taboada, M., Rossi, G., Yothers, G., Singer, C., Fein, L. E., Loman, N., Cameron, D., Campbell, C., Geyer, C. E.

المساهمون: Im, S-A

الوصف: Y ; 1

العلاقة: Annals of Oncology, Vol.33 No.5, pp.566-568; https://hdl.handle.net/10371/192284Test; 000797900700014; 179895

الإتاحة: https://doi.org/10.1016/j.annonc.2022.03.008Test
https://hdl.handle.net/10371/192284Test