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1

Strobeck, Matthew W., David N. Reisman, Ranjaka W. Gunawardena, Bryan L. Betz, Steven P. Angus, Karen E. Knudsen, Timothy F. Kowalik, Bernard E. Weissman, and Erik S. Knudsen. "Compensation of BRG-1 Function by Brm." Journal of Biological Chemistry 277, no. 7 (November 21, 2001): 4782–89. http://dx.doi.org/10.1074/jbc.m109532200.

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2

Miao, Ji, Sungsoon Fang, Jiyoung Lee, Clay Comstock, Karen E. Knudsen, and Jongsook Kim Kemper. "Functional Specificities of Brm and Brg-1 Swi/Snf ATPases in the Feedback Regulation of Hepatic Bile Acid Biosynthesis." Molecular and Cellular Biology 29, no. 23 (October 5, 2009): 6170–81. http://dx.doi.org/10.1128/mcb.00825-09.

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ABSTRACT Bile acid homeostasis is critical in maintaining health and is primarily regulated by the nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP). Bile acid-activated FXR indirectly inhibits expression of cholesterol 7α hydroxylase (CYP7A1), a key enzyme in conversion of cholesterol to bile acids, by induction of SHP. We recently demonstrated that SHP inhibits CYP7A1 transcription by recruiting chromatin-modifying cofactors, including Brm-Swi/Snf. Swi/Snf complexes contain either Brm or Brg-1 ATPases, and whether these subunits have distinct functions remains unclear. We have examined the role of these subunits in regulation of bile acid metabolism under physiological conditions by FXR and SHP. Brg-1 interacted with FXR and enhanced FXR-mediated transactivation of SHP, whereas Brm interacted with SHP and enhanced SHP-mediated repression of CYP7A1 and, interestingly, auto-repression of SHP. Chromatin immunoprecipitation and remodeling studies revealed that after treatment with FXR agonists, Brg-1 was recruited to the SHP promoter, resulting in transcriptionally active accessible chromatin, whereas Brm was recruited to both CYP7A1 and SHP promoters, resulting in inactive inaccessible chromatin. Our studies demonstrate that Brm and Brg-1 have distinct functions in the regulation of two key genes, CYP7A1 and SHP, within a single physiological pathway, feedback inhibition of bile acid biosynthesis, by differentially targeting SHP and FXR.
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3

Ma, Zhendong, Mi Jung Chang, Reesha Shah, Jill Adamski, Xueyan Zhao, and Etty N. Benveniste. "Brg-1 Is Required for Maximal Transcription of the Human Matrix Metalloproteinase-2 Gene." Journal of Biological Chemistry 279, no. 44 (August 17, 2004): 46326–34. http://dx.doi.org/10.1074/jbc.m405438200.

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Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases whose aberrant expression are correlated with tumor invasion and angiogenesis. The transcription factors Sp1, Sp3, and AP-2 are required for constitutive expression ofMMP-2in tumor cells; however, the regulatory mechanisms ofMMP-2expression are not well understood. We investigated the involvement of Brg-1, the ATPase subunit of the SWI/SNF complex, in human MMP-2 gene transcription. Reconstitution of Brg-1 enhancesMMP-2transcription in Brg-1-deficient SW-13 cells. Chromatin immunoprecipitation assay demonstrates that Brg-1 is required for recruitment of Sp1, AP-2, and polymerase II to the MMP-2 promoter, whereas the binding of Sp3 to the MMP-2 promoter is decreased upon Brg-1 reconstitution. Furthermore, Sp1 interacts with Brg-1in vivo. Restriction enzyme accessibility assays indicate that accessibility of the MMP-2 promoter region is not changed in the absence or presence of Brg-1. These results illustrate the connection between the SWI/SNF complex and optimal expression ofMMP-2and highlight the critical function of Brg-1 in regulating the recruitment of Sp1, Sp3, AP-2, and polymerase II to the MMP-2 promoter.
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4

DiRenzo, James, Yongfeng Shang, Michael Phelan, Säid Sif, Molly Myers, Robert Kingston, and Myles Brown. "BRG-1 Is Recruited to Estrogen-Responsive Promoters and Cooperates with Factors Involved in Histone Acetylation." Molecular and Cellular Biology 20, no. 20 (October 15, 2000): 7541–49. http://dx.doi.org/10.1128/mcb.20.20.7541-7549.2000.

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ABSTRACT Several factors that mediate activation by nuclear receptors also modify the chemical and structural composition of chromatin. Prominent in this diverse group is the steroid receptor coactivator 1 (SRC-1) family, which interact with agonist-bound nuclear receptors, thereby coupling them to multifunctional transcriptional coregulators such as CREB-binding protein (CBP), p300, and PCAF, all of which have potent histone acetyltransferase activity. Additionally factors including the Brahma-related gene 1 (BRG-1) that are involved in the structural remodeling of chromatin also mediate hormone-dependent transcriptional activation by nuclear receptors. Here, we provide evidence that these two distinct mechanisms of coactivation may operate in a collaborative manner. We demonstrate that transcriptional activation by the estrogen receptor (ER) requires functional BRG-1 and that the coactivation of estrogen signaling by either SRC-1 or CBP is BRG-1 dependent. We find that in response to estrogen, ER recruits BRG-1, thereby targeting BRG-1 to the promoters of estrogen-responsive genes in a manner that occurs simultaneous to histone acetylation. Finally, we demonstrate that BRG-1-mediated coactivation of ER signaling is regulated by the state of histone acetylation within a cell. Inhibition of histone deacetylation by trichostatin A dramatically increases BRG-1-mediated coactivation of ER signaling, and this increase is reversed by overexpression of histone deacetylase 1. These studies support a critical role for BRG-1 in ER action in which estrogen stimulates an ER–BRG-1 association coupling BRG-1 to regions of chromatin at the sites of estrogen-responsive promoters and promotes the activity of other recruited factors that alter the acetylation state of chromatin.
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5

Mudhasani, Rajini, and Joseph D. Fontes. "The Class II Transactivator Requires brahma-Related Gene 1 To Activate Transcription of Major Histocompatibility Complex Class II Genes." Molecular and Cellular Biology 22, no. 14 (July 15, 2002): 5019–26. http://dx.doi.org/10.1128/mcb.22.14.5019-5026.2002.

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ABSTRACT The class II transactivator (CIITA) is the key regulator of major histocompatibility complex (MHC) class II gene transcription. We demonstrate here that CIITA requires the ATPase subunit of an hSWI/SNF complex, brahma-related gene 1 (BRG-1), to activate transcription. When introduced into a cell line lacking BRG-1, CIITA was unable to activate cellular MHC class II genes. Reexpression of the wild-type but not an ATP-binding-deficient BRG-1 protein in this cell line restored the ability of CIITA to transactivate transcription of MHC class II genes. Interestingly, when the activity of CIITA was assayed in the BRG-1-deficient cell line by using a plasmid-based reporter assay, BRG-1 was not required for transcriptional activation, suggesting that the chromatin structure on the plasmid is such that BRG-1 is not necessary. Coimmunoprecipitation experiments were performed to determine if BRG-1 and CIITA proteins associate with each other in cells. We found that the two proteins coimmunoprecipitate and that amino acids 1 to 140 of CIITA are sufficient for binding. Taken together, these data suggest that BRG-1 and, very likely, an hSWI/SNF complex are required for transcription of MHC class II genes. The complex is likely recruited to MHC class II promoters, at least in part, by interaction with CIITA.
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6

Kutluay, Sebla B., Sarah L. DeVos, Jennifer E. Klomp, and Steven J. Triezenberg. "Transcriptional Coactivators Are Not Required for Herpes Simplex Virus Type 1 Immediate-Early Gene Expression In Vitro." Journal of Virology 83, no. 8 (January 28, 2009): 3436–49. http://dx.doi.org/10.1128/jvi.02349-08.

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ABSTRACT Virion protein 16 (VP16) of herpes simplex virus type 1 (HSV-1) is a potent transcriptional activator of viral immediate-early (IE) genes. The VP16 activation domain can recruit various transcriptional coactivators to target gene promoters. However, the role of transcriptional coactivators in HSV-1 IE gene expression during lytic infection had not been fully defined. We showed previously that transcriptional coactivators such as the p300 and CBP histone acetyltransferases and the BRM and Brg-1 chromatin remodeling complexes are recruited to viral IE gene promoters in a manner dependent mostly on the presence of the activation domain of VP16. In this study, we tested the hypothesis that these transcriptional coactivators are required for viral IE gene expression during infection of cultured cells. The disrupted expression of the histone acetyltransferases p300, CBP, PCAF, and GCN5 or the BRM and Brg-1 chromatin remodeling complexes did not diminish IE gene expression. Furthermore, IE gene expression was not impaired in cell lines that lack functional p300, or BRM and Brg-1. We also tested whether these coactivators are required for the VP16-dependent induction of IE gene expression from transcriptionally inactive viral genomes associated with high levels of histones in cultured cells. We found that the disruption of coactivators also did not affect IE gene expression in this context. Thus, we conclude that the transcriptional coactivators that can be recruited by VP16 do not contribute significantly to IE gene expression during lytic infection or the induction of IE gene expression from nucleosomal templates in vitro.
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7

Henderson, Angus, Adele Holloway, Raymond Reeves, and David John Tremethick. "Recruitment of SWI/SNF to the Human Immunodeficiency Virus Type 1 Promoter." Molecular and Cellular Biology 24, no. 1 (January 1, 2004): 389–97. http://dx.doi.org/10.1128/mcb.24.1.389-397.2004.

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ABSTRACT Following human immunodeficiency virus type 1 (HIV-1) integration into the host cell's genome, the 5′ long terminal repeat (LTR) is packaged into a highly specific chromatin structure comprised of an array of nucleosomes positioned with respect to important DNA sequence elements that regulate the transcriptional activity of the provirus. While several host cell factors have been shown to be important for chromatin remodeling and/or basal transcription, no specific mechanism that relieves the transcriptional repression imposed by nuc-1, a positioned nucleosome that impedes the start site of transcription, has been found. Since phorbol esters cause the rapid disruption of nuc-1 and markedly stimulate HIV-1 transcription, we looked for protein factors that associate with this region of the HIV-1 promoter in a phorbol-ester-dependent manner. We report here that ATF-3, JunB, and BRG-1 (the ATPase subunit of the 2-MDa human chromatin remodeling machine SWI/SNF) are recruited to the 3′ boundary of nuc-1 following phorbol myristate acetate stimulation in Jurkat T cells. Analysis of the recruitment of BRG-1 in nuclear extracts prepared from Jurkat T cells and reconstitution of an in vitro system with purified components demonstrate that ATF-3 is responsible for targeting human SWI/SNF (hSWI/SNF) to the HIV-1 promoter. Importantly, this recruitment of hSWI/SNF required HMGA1 proteins. Further support for this conclusion comes from immunoprecipitation experiments showing that BRG-1 and ATF-3 can exist together in the same complex. Although ATF-3 clearly plays a role in the specific targeting of BRG-1 to the HIV-1 promoter, the maintenance of a stable association between BRG-1 and chromatin appears to be dependent upon histone acetylation. By adding BRG-1 back into a BRG-1-deficient cell line (C33A cells), we demonstrate that trichostatin A strongly induces the 5′-LTR-driven reporter transcription in a manner that is dependent upon BRG-1 recruitment.
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8

Wee, G., D. B. Koo, J. S. Kim, B. S. Song, J. S. Park, X. L. Jin, Y. Y. Lee, Y. M. Han, and K. K. Lee. "156 DIFFERENTIAL REORGANIZATION OF HISTONE ACETYLATION THROUGH ATP-DEPENDENT REMODELING FACTOR DURING PRONUCLEAR FORMATION IN PORCINE ZYGOTIC CHROMATINS." Reproduction, Fertility and Development 19, no. 1 (2007): 195. http://dx.doi.org/10.1071/rdv19n1ab156.

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ATP-dependent remodeling complexes and histone acetyltransferase/deacetylase complexes in chromatin modification can be characterized by the use of energy from ATP hydrolysis or covalent modification. But they have similar functions during the transcriptional process. After fertilization, histone acetylation in paternal and maternal chromatin is reprogrammed to obtain transcriptional activity during chromatin remodeling such as decondensation. However, these mechanisms in zygotic chromatin are poorly understood. In the present study, the reorganization process of histone H4 acetylation after fertilization was investigated through co-localization in the nucleus of ATP-dependent remodeling factors and histone acetyltransferases during parental chromatin decondensation. The molecules were monitored by immunofluorescence analysis with specific antibodies directed against AcH4K5, HAT1, P300, Tip60, Brg-1, and Mi-2. Fluorescence signals of Brg-1 and Mi-2 in porcine embryonic fibroblasts and HeLa cells co-localized with chromatin during interphase and M phase, although the Mi-2 signal existed around chromosomes at metaphase. However, Brg-1 and Mi-2 in porcine oocytes did not interact with chromosomes during meiosis, despite their existence in the oocyte cytoplasm. At 6 h after fertilization, signals of Brg-1 and Mi-2 were observed in most parental chromatin and remained until syngamy of the pronuclear stage. In histone acetylation and chromatin remodeling, acetylation of H4K5 was generated from sperm chromatin at 4 h after fertilization and preceded the appearance of Brg-1. Additionally, HAT1 showed stronger intensities compared with P300 and Tip60, correlating with acetylated-H4K5, and also appeared earlier than Brg-1. In contrast to that in sperm chromatin, Brg-1 in maternal chromatin anteceded HAT1. Consequently, paternal chromatin remodeling was completed after histone acetylation, but maternal chromatin remodeling was preceded by histone acetylation. Our findings indicate that paternal and maternal chromatin undergo differential remodeling and reprogramming during pronuclear formation, suggesting that gene expression in the chromatin of each parent may be regulated separately.
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9

Camidge, D. Ross, Hye Ryun Kim, Myung-Ju Ahn, James Chih-Hsin Yang, Ji-Youn Han, Maximilian Hochmair, Ki Hyeong Lee, et al. "Association of depth of target lesion response to brigatinib with outcomes in patients with ALK inhibitor-naive ALK+ NSCLC in ALTA-1L." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): 9072. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.9072.

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9072 Background: In patients (pts) with crizotinib (CRZ)-refractory advanced ALK+ NSCLC in the phase 2 ALTA trial (NCT02094573), the depth of target lesion response to brigatinib (BRG) correlated with PFS and OS. Here, we examine the association of maximum decrease in target lesions with PFS and OS in ALTA-1L (NCT02737501), a randomized phase 3 trial of BRG vs CRZ in pts with ALK inhibitor-naive advanced ALK+ NSCLC. Methods: Pts were randomized 1:1 to receive BRG 180 mg qd (7-day lead-in at 90 mg; n=137) or CRZ 250 mg bid (n=138). Pts with target lesion assessment by blinded independent review committee (BIRC) were grouped based on greatest decrease from baseline per RECIST v1.1: none–50%, 51%–75%, and 76%–100% shrinkage. Outcomes in the ≤50% target lesion shrinkage group served as the comparator for outcomes in the 51%–75% and 76%–100% groups. Results: At study end (last pt contact: Jan 29, 2021), 124/137 pts in the BRG arm and 125/138 pts in the CRZ arm had ≥1 evaluable target lesion assessment; female (BRG/CRZ), 51%/59%; median age, 57.5/60.0 years. Median follow-up was 40.8/15.7 months. In BRG/CRZ arms, 76%-100% shrinkage was observed in 56%/34% of pts, 51%-75% shrinkage in 27%/30%, and ≤50% shrinkage in 16%/35%, respectively. BRG was associated with significantly more pts with target lesion shrinkage >75% vs CRZ ( P=0.0005), and a Cochran-Armitage trend analysis demonstrated significantly deeper response across all shrinkage groups for BRG compared with CRZ ( P<0.0001). A majority of pts in the BRG arm experienced 76%–100% target lesion shrinkage in all subgroups analyzed. Pts treated with BRG or CRZ with target lesion shrinkage >50% had lower risk of a PFS event (BRG HR [95% CI]: 51%–75% shrinkage, 0.58 [0.29–1.18]; 76%–100%, 0.23 [0.12–0.46]; CRZ: 51%–75% shrinkage, 0.68 [0.41–1.12]; 76%–100%, 0.26 [0.15–0.45]) or an OS event (BRG: 51%–75% shrinkage, 0.39 [0.17–0.89]; 76%–100%, 0.15 [0.07–0.35]; CRZ: 51%–75% shrinkage, 0.43 [0.21–0.85]; 76%–100%, 0.23 [0.10–0.50]) than pts with ≤50% shrinkage. Longer median time to PFS and OS and higher 4-year estimated OS rates were associated with depth of response in both arms (Table). Conclusions: In this exploratory post hoc analysis, BRG demonstrated significantly deeper target lesion response vs CRZ. Pts with >75% shrinkage had significantly reduced risk of a PFS or OS event vs pts with ≤50% target lesion shrinkage. Clinical trial information: NCT02737501. [Table: see text]
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10

Ahn, Myung-Ju, HyeRyun Kim, James Chih-Hsin Yang, Ji-Youn Han, Jong Seok Lee, Maximilian J. Hochmair, Jacky Yu-Chung Li, et al. "Brigatinib (BRG) versus crizotinib (CRZ) in Asian versus non-Asian patients (pts) in the phase III ALTA-1L trial." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 9026. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.9026.

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9026 Background: We report an analysis of BRG vs CRZ in Asian vs non-Asian pts with ALK inhibitor–naive, ALK+ NSCLC from ALTA-1L (NCT02737501). Methods: Pts were randomized 1:1 to BRG 180 mg QD (7-day lead-in at 90 mg) or CRZ 250 mg BID. Primary endpoint: blinded independent review committee (BIRC)-assessed PFS (RECIST v1.1). Secondary efficacy endpoints: BIRC-assessed ORR, intracranial (i) ORR, and iPFS. Results: 275 pts were randomized; 108 Asian (BRG/CRZ, n = 59/49), 167 non-Asian (n = 78/89); median age: Asian, 55/56 y; non-Asian, 60/60 y. 32/24% of Asians vs 22/28% of non-Asians received prior chemotherapy for advanced disease; 36/33% vs 24/28% had baseline CNS metastases. As of 19 Feb 2018, median follow-up was 10.1/10.0 mo (BRG/CRZ) in Asians vs 11.0/9.0 mo in non-Asians, with 12 vs 20 PFS events in Asians and 24 vs 43 in non-Asians. In Asians, median BIRC-assessed PFS (mo) was not reached (NR; 95% CI 11.2–NR) with BRG vs 11.1 (9.2–NR) with CRZ (HR 0.41 [95% CI 0.20–0.86]; log-rank P= 0.0261); in non-Asians, BRG PFS was NR (NR) vs 9.4 (7.3–NR) with CRZ (HR 0.54 [0.33–0.90]; log-rank P= 0.0132) (Table). AE profile of each drug was similar in Asians vs non-Asians. Most common any-grade AEs (≥25%) in Asians in BRG arm: diarrhea; elevated blood CPK, ALT, and AST. Discontinuation due to AE (BRG/CRZ): 8.5/6.3% in Asian pts; 14.3/10.1% in non-Asian pts. Conclusions: BRG showed comparable improvement in PFS vs CRZ both in Asians and non-Asians in ALK inhibitor–naive ALK+ NSCLC. Clinical trial information: NCT02737501. [Table: see text]
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11

Wang, S. "Prohibitin requires Brg-1 and Brm for the repression of E2F and cell growth." EMBO Journal 21, no. 12 (June 17, 2002): 3019–28. http://dx.doi.org/10.1093/emboj/cdf302.

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12

Susanto, Sri Nurhari, and Kadek Cahya Susila Wibawa. "The Existence of The Indonesia Peatland Restoration Agency in Perspective of Organization and Authority." Administrative Law and Governance Journal 3, no. 1 (March 5, 2020): 92–103. http://dx.doi.org/10.14710/alj.v3i1.92-103.

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The Indonesia Peatland Restoration Agency (BRGI) is established with the legal basis of Presidential Regulation Number 1 Year 2016. BRGI is founded by coordinating and facilitating peatland restoration in several regions in Indonesia. BRGI is a non-structural institution which is under responsible to the President. BRGI is a state's auxiliary organ (agency or supporting / supporting body). In authority, BRGI can expand its tasks and functions given by the Presidential Regulation or outside the Article 2 and 3 of Presidential Regulation No. 1 2016. Article 30 section (1) clearly states that BRG conducts the duties for 5 (five) years and ends on December 31st, 2020. This is further strengthened by the provision of Article 31 which states that the Presidential Regulation is valid for five years from the enactment. The President with his prerogative has the authority whether to continue the existence of the BRGI or not, even though the Presidential Regulation clearly states the expiration of the institution. Keyword: The Indonesia Peatland Restoration Agency (BRGI), authority, prerogative. Abstrak Badan Restorasi Lahan Gambut Indonesia (BRGI) didirikan dengan dasar hukum Peraturan Presiden Nomor 1 Tahun 2016. BRGI didirikan dengan mengoordinasi dan memfasilitasi restorasi lahan gambut di beberapa daerah di Indonesia. BRGI adalah lembaga non-struktural yang bertanggung jawab kepada Presiden. BRGI adalah organ bantu negara (lembaga atau badan pendukung / pendukung). Dalam wewenangnya, BRGI dapat memperluas tugas dan fungsinya yang diberikan oleh Peraturan Presiden atau di luar Pasal 2 dan 3 Peraturan Presiden No. 1 2016. Pasal 30 ayat (1) dengan jelas menyatakan bahwa BRG melaksanakan tugas selama 5 (lima) tahun dan berakhir pada tanggal 31 Desember 2020. Hal ini semakin diperkuat dengan ketentuan Pasal 31 yang menyatakan bahwa Peraturan Presiden ini berlaku selama lima tahun sejak berlakunya. Presiden dengan hak prerogatifnya memiliki wewenang apakah akan melanjutkan keberadaan BRGI atau tidak, meskipun Peraturan Presiden dengan jelas menyatakan berakhirnya lembaga. Kata kunci: Badan Restorasi Lahan Gambut Indonesia (BRGI), otoritas, hak prerogatif.
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13

Bazhenova, Lyudmila, Scott N. Gettinger, Corey J. Langer, Ravi Salgia, Kathryn A. Gold, Rafael Rosell, Alice Tsang Shaw, et al. "Brigatinib (BRG) in patients (pts) with ALK+ non-small cell lung cancer (NSCLC): Updates from a phase 1/2 trial." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e20682-e20682. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e20682.

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e20682 Background: The investigational next-generation ALK inhibitor BRG has shown activity in ALK+ NSCLC pts in a phase 1/2 trial; here, we provide updated data with longer follow-up. Methods: In this ongoing phase 1/2, single-arm, open-label, multicenter trial (NCT01449461), pts with advanced malignancies (including ALK+ NSCLC) received oral BRG (30–300 mg/d). Activity by RECIST v1.1 in ALK+ NSCLC pts and safety in all pts are shown. Results: 58% (79/137) pts had ALK+ NSCLC, with median age 54 y; of these, 90% (71/79) had received crizotinib (CRZ). As of May 31, 2016, 41% (32/79) ALK+ NSCLC pts continued to receive BRG; median treatment duration was 20.0 mo (1 d–47.4 mo). The table shows efficacy in CRZ-treated pts; median overall survival was 47.6 mo (95% CI 21.4–47.6 mo). All 8 CRZ-naive pts had confirmed objective responses; median duration of response and progression-free survival (PFS) were not reached. In a post hoc analysis, 53% (95% CI 27%–79%; 8/15) ALK+ NSCLC pts with measurable baseline brain metastases had confirmed intracranial objective responses (last scan date: October 8, 2015). Median intracranial PFS in 46 evaluable ALK+ NSCLC pts with baseline brain metastases was 14.6 mo (95% CI 12.7–36.8 mo). Treatment-emergent adverse events (AEs) in ≥30% of all pts, mainly grade 1/2, were nausea 53%, fatigue 45%, diarrhea 42%, headache 35%, and cough 33%; serious treatment-emergent AEs in ≥5% of pts were pneumonia 7%, dyspnea 6%, and hypoxia 5%. 10% of pts (14/137) discontinued BRG due to an AE. Conclusions: BRG yielded substantial whole-body and intracranial activity in ALK+ NSCLC pts in this trial, with acceptable safety. These data informed design of the pivotal randomized phase 2 trial of BRG (90 mg qd or 180 mg qd [with lead-in]) in CRZ-refractory ALK+ NSCLC (ALTA). Clinical trial information: NCT01449461. [Table: see text]
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Rao, Mahadev, Mathew C. Casimiro, Michael P. Lisanti, Mark D'Amico, Chenguang Wang, L. Andrew Shirley, Jennifer E. Leader, et al. "Inhibition of cyclin D1 gene transcription by Brg-1." Cell Cycle 7, no. 5 (March 2008): 647–55. http://dx.doi.org/10.4161/cc.7.5.5446.

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15

Tiseo, Marcello, Sanjay Popat, Scott N. Gettinger, Solange Peters, Jeff Haney, David Kerstein, and D. Ross Camidge. "Design of ALTA-1L (ALK in lung cancer trial of brigatinib in first-line), a randomized phase 3 trial of brigatinib (BRG) versus crizotinib (CRZ) in tyrosine kinase inhibitor (TKI)-naive patients (pts) with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): TPS9098. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.tps9098.

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TPS9098 Background: BRG is an investigational, next-generation ALK inhibitor with potent preclinical activity against rearranged ALK and CRZ-resistant mutants. In an ongoing phase 1/2 trial, BRG has shown promising intracranial and whole-body activity in ALK+ NSCLC pts with or without prior CRZ therapy ( Lancet Oncol. 2016;17:1683-96). In an ongoing pivotal randomized phase 2 trial (ALTA) evaluating 2 BRG regimens (90 mg qd and 180 mg qd with a 7-d lead-in at 90 mg), BRG has shown substantial objective response rates (ORRs) and robust progression-free survival (PFS) in pts with CRZ-resistant ALK+ NSCLC, particularly at 180 mg (with lead-in), and acceptable safety ( J Thorac Oncol. 2017;12:S612-3). Based on these results, the ALTA-1L trial was designed to assess the efficacy and safety of BRG vs CRZ in pts with advanced ALK+ NSCLC naive to TKI therapy (including ALK inhibitors). Methods: ALTA-1L (NCT02737501) is an open-label, multicenter, randomized phase 3 trial. Pts (≥18 y of age) are required to have locally advanced or metastatic ALK+ NSCLC, no prior TKI therapy, and ≤1 prior systemic anticancer regimen in the advanced setting. Approximately 270 pts will be stratified by presence of brain metastases at baseline and prior chemotherapy (yes/no) and randomized 1:1 to receive oral BRG (180 mg qd with a 7-d lead-in at 90 mg) or CRZ (250 mg bid). The primary endpoint is PFS per RECIST v1.1 assessed by a blinded independent review committee (BIRC); secondary endpoints include ORR, duration of response, overall survival, safety/tolerability, pt-reported outcomes, and intracranial ORR/PFS. The primary endpoint will be analyzed with the Kaplan-Meier method and a 2-sided stratified log-rank test after 198 events; 2 interim analyses are planned after approximately 50% and 75% of expected events. CRZ-treated pts may cross over to BRG (180 mg [with lead-in]) after BIRC-assessed disease progression. ALTA-1L was initiated in April 2016; 150 sites are planned in North America, Europe, and the Asia-Pacific region. 97 pts were enrolled as of February 6, 2017. Clinical trial information: NCT02737501.
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Omo-Ogboi, A. C., W. Wang, and B. Zhao. "The first case of BRG (SMARCA4)/INI Deficient Tracheal Carcinoma: A Case Report and Review of the Literature." American Journal of Clinical Pathology 156, Supplement_1 (October 1, 2021): S150—S151. http://dx.doi.org/10.1093/ajcp/aqab191.320.

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Abstract Introduction/Objective Primary tumors of the trachea are rare, they account for less than 0.1% of tumors in humans. In adults, 90% of primary tracheal tumors are malignant, with squamous cell carcinoma and adenoid cystic carcinoma accounting for two-thirds, with other forms occurring less frequently. The BRG (SMARCA4)/INI deficient tumor is a relatively new defined entity which is recently introduced in the WHO Classification of Tumors, 5th edition, 2021. The gene SMARCA4 is located at 19p13. Loss of SMARCA4 has been reported in several aggressive tumors with high- grade undifferentiated rhabdoid morphology but has not been reported in the trachea. Hence, we report the first case of BRG (SMARCA4)/ INI deficient tracheal carcinoma. Methods/Case Report We present a 60-year-old male with a history of tobacco abuse, shortness of breath, and a tracheal mass on chest imaging. Bronchoscopy was performed and showed a fleshy friable lesion at the anterior trachea with evidence of blood dripping into the distal airways. Results (if a Case Study enter NA) Microscopic examination showed a high grade, poorly differentiated carcinoma with tumor necrosis, high mitotic counts, and marked nuclear pleomorphism. Immunohistochemical stains were performed. The tumor cells were strongly and diffusely positive for CK-7 and weakly positive for synaptophysin, negative for pan-cytokeratin, TTF-1, CK-20, p40, CK5/6, and chromogranin. Then BRG (SMARCA4) and INI 1 (BAR47) were performed and showed negative staining on BRG expression, while INI 1 is intact (nuclear expression). These features are consistent with BRG (SMARCA4)/ INI deficient carcinoma. Conclusion BRG (SMARCA4)/ INI deficient carcinoma is a new entity in the trachea, which is very aggressive with a poor prognosis. Targeted therapy or clinical trials may be available as additional cases are diagnosed in the future.
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Pham, Lan V., Archito Tamayo, Hai-Jun Zhou, Yen-Chiu Lin-Lee, Lingchen Fu, and Richard J. Ford. "Recruitment of the SWI/SNF Chromatin Remodeling Complex by NFATc1 in the Transcriptional Regulation of the C-MYC Oncogene in Aggressive B-Cell Lymphomas." Blood 112, no. 11 (November 16, 2008): 3808. http://dx.doi.org/10.1182/blood.v112.11.3808.3808.

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Abstract The NFAT (nuclear factor of activated T-cells) family of transcription factors functions as integrators of multiple signaling pathways by binding to chromatin in combination with other transcription factors and coactivators to regulate genes central for cell growth and survival in hematopoietic cells. Recent experimental evidence has implicated the calcineurin/NFAT signaling pathway for involvement in the pathogenesis of various malignancies, including large B-cell lymphoma (LBCL), a non-Hodgkin’s lymphoma subgroup that is generally responsive to conventional cancer therapies (R-CHOP), but relapse is common that subsequently leads to therapeutic resistance. Although we have shown previously that NFAT family member NFATc1 is constitutively activated and has the ability to maintain cell growth and survival in LBCL cell lines and primary cells, the molecular mechanism(s) underlying how NFATc1 regulates cell growth and survival in LBCL is still unclear. In this study, we demonstrate that the well-known oncogene c-myc is transcriptionally regulated by the transcription factor NFATc1 in LBCL, through a chromatin remodeling mechanism that involves the recruitment of the SWI/SNF chromatin-remodeling complex. In aggressive B-cell lymphoma cell lines, c-myc oncogene protein expression was shown to correlate with NFATc1 protein expression. We further showed that NFATc1 binds to a specific DNA binding element within the proximal c-myc promoter and up-regulates c-myc transcription. The SWI/SNF proteins Brg-1 and Brm, chromatin-remodeling proteins that utilize ATP hydrolysis for energy to modify chromatin structure in order to regulate gene expression, also were shown to bind to the NFAT binding site on the c-myc promoter. Confocal microscopic analysis showed that NFATc1 colocalizes with Brg-1, and co-immunoprecipitation assays showed that Brg-1 interacts with NFATc1. Both proteins interact with the c-myc promoter within the NFAT binding site, as demonstrated by chromatin-immunoprecipitation (ChIP) analysis. Induction of a constitutively active mutant of NFATc1 (caNFATc1) in an NFATc1 negative lymphoma cell line induces c-myc protein expression. Constitutively active NFATc1 also enhances Brg-1 binding to the c-myc promoter when analyzed by ChIP-qPCR assays, suggesting that NFATc1 recruits Brg-1 to the NFAT binding site in the c-myc promoter. Down-regulation of NFATc1 by chemical inhibitors (FK-506) or by validated shRNA of NFATc1, inhibited c-myc protein expression and in-vitro lymphoma cell growth. Our data indicates a novel control mechanism for the transcriptional regulation of c-myc in the pathophysiology of aggressive lymphoma B cells and suggests that targeting NFATc1 could have therapeutic value.
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18

Gettinger, Scott N., Rudolf M. Huber, Dong-Wan Kim, Lyudmila Bazhenova, Karin Holmskov Hansen, Marcello Tiseo, Corey J. Langer, et al. "Brigatinib (BRG) in ALK+ crizotinib (CRZ)-refractory non-small cell lung cancer (NSCLC): Final results of the phase 1/2 and phase 2 (ALTA) trials." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 9071. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.9071.

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9071 Background: BRG is a kinase inhibitor approved for the treatment of patients (pts) with ALK+ metastatic NSCLC; specific details for BRG use vary by indication and country. We report long-term efficacy and safety results of the Phase 1/2 and Phase 2 (ALTA) trials of BRG. Methods: The Phase 1/2 study was a single-arm, open-label trial (NCT01449461) of BRG 30–300 mg/d in pts with advanced malignancies. ALTA (NCT02094573) randomized pts with CRZ-refractory ALK+ NSCLC to receive BRG at 90 mg qd (arm A) or 180 mg qd with 7-d lead-in at 90 mg (arm B). For the Phase 1/2 study, investigator assessments of confirmed objective response rate (cORR; RECIST v1.1), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety in pts with ALK+ NSCLC are reported. The primary endpoint of ALTA was cORR per investigator; secondary endpoints included cORR per independent review committee (IRC), DoR, PFS, and OS. Results: In the Phase 1/2 study, 137 pts received BRG; of these, 79 pts had ALK+ NSCLC (71/79 had prior CRZ; 28/79 received 180 mg qd [7-d lead-in at 90 mg]; 14/79 received 90 mg qd). In ALTA, 222 pts with CRZ-refractory ALK+ NSCLC were randomized (n = 112/110, arm A/B). At the end of the Phase 1/2 study (Feb 18, 2020), with median 27.7 mo follow-up (̃67 mo after last pt enrolled), 4 pts remained on BRG. At the end of ALTA (Feb 27, 2020), with median 19.6/28.3 mo follow-up in arm A/B (̃53 mo after last pt enrolled), 10/17 pts in arm A/B were still on treatment. Table shows efficacy results from final analyses with long-term follow-up. In ALTA, the IRC-assessed intracranial cORR in pts with measurable baseline brain metastases was 50% (13/26) in arm A and 67% (12/18) in arm B; Kaplan-Meier (KM) estimated median intracranial DoR was 9.4 mo (95% CI, 3.7, not reached [NR]) in arm A and 16.6 mo (3.7, NR) in arm B. With long-term follow-up, no new safety signals were identified. Treatment-emergent adverse events led to dose interruption (Phase 1/2: 59%; ALTA arm A/B: 49%/61%), dose reduction (13%; 8%/33%), or discontinuation (10%; 4%/13%). Conclusions: BRG showed sustained long-term activity, PFS, and manageable safety in pts with CRZ-refractory ALK+ NSCLC. The 180 mg/d dose after 7-d lead-in at 90 mg/d led to numerically higher median PFS and OS. Final results are similar to those reported for other approved ALK tyrosine kinase inhibitors in this setting. Clinical trial information: NCT01449461, NCT02094573. [Table: see text]
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19

Bazhenova, Lyudmila, J. Graeme Hodgson, Corey J. Langer, George R. Simon, Scott N. Gettinger, Sai-Hong Ignatius Ou, Karen L. Reckamp, et al. "Activity of brigatinib (BRG) in crizotinib (CRZ)-resistant ALK+ NSCLC patients (pts) according to ALK plasma mutation status." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 9065. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.9065.

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9065 Background: BRG is a potent and selective ALK inhibitor with preclinical and clinical activity against wild-type ALK and a broad range of mutants associated with clinical CRZ resistance, including G1202R. Herein we examine the association between BRG efficacy and ALK mutation status using plasma specimens from the initiation of BRG treatment (baseline [BL]) and the end of BRG treatment (EOT) in CRZ-resistant ALK+ NSCLC pts enrolled in the BRG Ph1/2 or pivotal Ph2 (ALTA) trials. Methods: Plasma samples were analyzed using the Resolution Bioscience ctDx Lung Panel v3.0. BRG activity was described using the confirmed objective response rate (cORR) (RECIST v1.1). Data are reported as of May 31, 2016 for the Ph1/2 (NCT01449461) and ALTA (NCT02094573) trials. Results: Of 291 CRZ-resistant ALK+ NSCLC pts enrolled in the Ph1/2 (N = 69) and ALTA (N = 222) trials, evaluable plasma samples were obtained from 67 pts at BL. cORR to BRG in these pts was 49% (33/67). An ALK fusion was detected in plasma in 45% (30/67) of these pts (cORR 57% [17/30]), of whom 33% (10/30) had secondary ALK mutations (cORR 50% [5/10]) and 67% (20/30) did not (cORR 60% [12/20]). Best responses in pts with secondary ALK mutations were: 2 CR (ALK amplification [Amp] copy number [CN] = 10; T1151M); 3 PR (L1196M; E1408V; Amp CN = 6); 4 SD (L1196M; E1419K; F1174C; C1156Y+S1206F+G1269A); 1 PD (T1151R+C1156Y+E1161D+F1174L). Of 67 pts with evaluable plasma at BL, 35 discontinued BRG therapy, of whom 20 had evaluable samples collected at EOT. No new mutations were detected at EOT in 75% (15/20) of pts. Complex mutation patterns were associated with resistance in the remaining 25% (5/20): High-level ALK-Amp (CN = 58); ALK-Amp (CN = 14)+MET-Amp (CN = 6); ALK-S1206F+S1206C+Amp (CN = 6); ALK-G1202R+L1196M+L1198Q; ALK-G1202R+BRAF-V600E+KRAS-G12D. Conclusions: ALK fusions were detected in plasma in < 50% of CRZ-resistant ALK+ NSCLC pts. BRG had substantial activity in ALK fusion–positive pts with a range of CRZ-resistance mutations. Neither primary nor secondary resistance to BRG was associated with any single plasma ALK mutation. The therapeutic implications of complex secondary resistance patterns associated with BRG require further exploration. Clinical trial information: NCT01449461, NCT02094573.
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Vaštakaitė-Kairienė, Viktorija, Aušra Brazaitytė, Jurga Miliauskienė, Rūta Sutulienė, Kristina Laužikė, Akvilė Viršilė, Giedrė Samuolienė, and Erik S. Runkle. "Photon Distribution of Sole-Source Lighting Affects the Mineral Nutrient Content of Microgreens." Agriculture 12, no. 8 (July 23, 2022): 1086. http://dx.doi.org/10.3390/agriculture12081086.

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In the study, we cultivated basil, beet, and mustard microgreens under different lighting treatments from light-emitting diodes (LEDs) and evaluated the contents of mineral nutrients. Microgreens grew under blue 447, red 638 and 665, far-red 731 nm LEDs, or the same spectrum but with partial substitution of 638 nm red with green 520 (BRG), yellow 595 (BRY), or orange 622 nm (BRO) LEDs (16 h photoperiod; total photon flux density of 300 μmol m −2 s −1). BRG, BRY, or BRO lighting had distinct effects on mineral contents among the microgreen species. BRG increased the content of mineral nutrients, especially in mustard and beet. In all microgreens, Ca and P were associated with BRG; in beet and mustard, Zn and Mg were associated with BRG; in basil, Zn was associated with BRY and Mg with BRO treatments. A broader photon spectrum increased Fe (up to 2.9–fold), K:Ca, P:Mg, and P:Zn in basil, and Fe:Zn in microgreens. We conclude that the partial replacement of red with green light was the most effective at enhancing the mineral nutrient content of microgreens, although responses varied among the crops studied.
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21

Reckamp, Karen L., Joseph Lee, Joice Huang, Irina Proskorovsky, William Reichmann, Mira Krotneva, David Kerstein, and Hui Huang. "Matching-adjusted indirect comparison (MAIC) of relative efficacy for brigatinib vs. ceritinib and alectinib in crizotinib-resistant anaplastic lymphoma kinase (ALK+) non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e20675-e20675. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e20675.

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e20675 Background: Brigatinib (BRG), ceritinib (CER), and alectinib (ALEC) are second-generation ALK inhibitors developed for crizotinib (CRZ)-resistant ALK+ NSCLC. No randomized trial has directly compared the efficacy of these treatments. The goal of this analysis was to use an MAIC to indirectly compare progression-free survival (PFS) and overall survival (OS) for BRG vs CER and BRG vs ALEC in CRZ-resistant ALK+ NSCLC patients (pts). Methods: This analysis used pt-level data from arm B (180 mg qd with a 7-day lead-in at 90 mg, n=110) of the ALTA trial for BRG and published summary data from ASCEND-1/ASCEND-2 and NP28673 trials for CER and ALEC, respectively. PFS and OS curves from published data were digitized to generate virtual pt-level data for estimation of event rates. Pts in ALTA were assigned weights so that their weighted mean baseline characteristics matched baseline characteristics in each of ASCEND-1, ASCEND-2, and NP28673. Relative treatment effects pre- and post-matching were estimated using Cox proportional hazards models. Results: Prior to matching, baseline imbalances were noted in ECOG PS 2, prior chemotherapy, Asian race, smoking status, and best prior response to CRZ among trials. Weighting reduced effective sample sizes (ESSs) for ALTA pts in the matched comparisons. Relative efficacy results were robust and did not appreciably change after adjusting for the prognostic factors (Table 1). Conclusions: Both before and after matching, BRG had significantly longer PFS compared to CER and ALEC, significantly longer OS than CER, and a trend toward longer OS than ALEC. [Table: see text]
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Papadopoulos, Natalia, Johan Lennartsson, and Carl-Henrik Heldin. "PDGFRβ translocates to the nucleus and regulates chromatin remodeling via TATA element–modifying factor 1." Journal of Cell Biology 217, no. 5 (March 15, 2018): 1701–17. http://dx.doi.org/10.1083/jcb.201706118.

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Translocation of full-length or fragments of receptors to the nucleus has been reported for several tyrosine kinase receptors. In this paper, we show that a fraction of full-length cell surface platelet-derived growth factor (PDGF) receptor β (PDGFRβ) accumulates in the nucleus at the chromatin and the nuclear matrix after ligand stimulation. Nuclear translocation of PDGFRβ was dependent on PDGF-BB–induced receptor dimerization, clathrin-mediated endocytosis, β-importin, and intact Golgi, occurring in both normal and cancer cells. In the nucleus, PDGFRβ formed ligand-inducible complexes with the tyrosine kinase Fer and its substrate, TATA element–modifying factor 1 (TMF-1). PDGF-BB stimulation decreased TMF-1 binding to the transcriptional regulator Brahma-related gene 1 (Brg-1) and released Brg-1 from the SWI–SNF chromatin remodeling complex. Moreover, knockdown of TMF-1 by small interfering RNA decreased nuclear translocation of PDGFRβ and caused significant up-regulation of the Brg-1/p53-regulated cell cycle inhibitor CDKN1A (encoding p21) without affecting PDGFRβ-inducible immediate-early genes. In conclusion, nuclear interactions of PDGFRβ control proliferation by chromatin remodeling and regulation of p21 levels.
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23

Strobeck, M. W., K. E. Knudsen, A. F. Fribourg, M. F. DeCristofaro, B. E. Weissman, A. N. Imbalzano, and E. S. Knudsen. "BRG-1 is required for RB-mediated cell cycle arrest." Proceedings of the National Academy of Sciences 97, no. 14 (July 5, 2000): 7748–53. http://dx.doi.org/10.1073/pnas.97.14.7748.

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24

Ahn, Myung-Ju, D. Ross Camidge, Marcello Tiseo, Karen L. Reckamp, Karin Holmskov Hansen, Sang-We Kim, Rudolf M. Huber, et al. "Brigatinib (BRG) in crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC): Updates from ALTA, a pivotal randomized phase 2 trial." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e20503-e20503. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e20503.

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e20503 Background: Most ALK+ NSCLC patients (pts) receiving CRZ eventually experience disease progression. Based on promising activity in a phase 1/2 trial, a randomized phase 2 trial of the ALK inhibitor BRG in pts with CRZ-refractory, advanced ALK+ NSCLC (ALTA; NCT02094573) was initiated. Responses and adverse events (AEs) varied with starting dose; therefore, ALTA was designed to evaluate 2 distinct BRG regimens. Methods: Pts were stratified by presence of baseline (BL) brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Primary endpoint was investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1. Results: In 222 pts (arm A/B, n=112/n=110), median age was 51/57 y; 71%/67% had brain metastases. As of May 31, 2016, 51%/56% (A/B) continued to receive BRG; median follow-up was 10.2/11.0 mo. Table shows efficacy. In pts with measurable BL brain metastases (A/B, n=26/n=18), confirmed intracranial ORR was 46%/67%. Most common treatment-emergent AEs (A/B) were: nausea 36%/43%, diarrhea 21%/39%, cough 23%/36%, headache 28%/30%, vomiting 28%/26%; grade ≥3 AEs included increased CPK 3%/10%, hypertension 6%/6%, pneumonia 3%/5%, increased lipase 5%/3%. A subset of pulmonary AEs with early onset (median: Day 2) occurred in 14/219 (6%) treated pts (3%, grade ≥3); 7/14 pts were successfully retreated. Dose reductions (8%/23%, A/B) and discontinuations (3%/10%) due to AEs were reported. Conclusions: BRG showed substantial activity, robust PFS, and acceptable safety at both dose levels, with numerically improved efficacy (particularly PFS and intracranial ORR) at 180 mg (with lead-in). Clinical trial information: NCT02094573. [Table: see text]
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Kim, Hyung Joong, Tae Kyu Oh, Yoon Hee Kim, Jaesun Lee, Joo Myung Moon, Yong Sun Park, and Chang Min Sung. "Pharmacokinetics of Ginsenoside Rb1, Rg3, Rk1, Rg5, F2, and Compound K from Red Ginseng Extract in Healthy Korean Volunteers." Evidence-Based Complementary and Alternative Medicine 2022 (January 24, 2022): 1–10. http://dx.doi.org/10.1155/2022/8427519.

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Individual differences in ginsenoside pharmacokinetics following ginseng administration in humans are still unclear. We aimed to investigate the pharmacokinetic properties of various ginsenosides, including Rb1, Rg3, Rg5, Rk1, F2, and compound K (CK), after a single oral administration of red ginseng (RG) and bioconverted red ginseng extract (BRG). This was a randomized, open-label, single-dose, single-sequence crossover study with washout every 1 week, and 14 healthy Korean men were enrolled. All subjects were equally assigned to two groups and given RG or BRG capsules. The pharmacokinetic parameters of ginsenosides were measured from the plasma drug concentration–time curve of individual subjects. Ginsenosides Rg3, Rk1 + Rg5, F2, and CK in the BRG group showed a higher Cmax, AUC(0–t), and AUC(0–∞) and shorter Tmax (for CK) than those in the RG group. These results suggest that BRG may lead to a higher absorption rate of bioactive ginsenosides. This study provides valuable information on the pharmacokinetics of various bioactive ginsenosides, which is needed to enhance the therapeutic efficacy and pharmacological activity of ginseng.
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Ou, Sai-Hong Ignatius, Marcello Tiseo, D. Ross Camidge, Myung-Ju Ahn, Rudolf M. Huber, Maximilian J. Hochmair, Sang-We Kim, et al. "Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC) and brain metastases in the pivotal randomized phase 2 ALTA trial." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e20502-e20502. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e20502.

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e20502 Background: The CNS is often a site of first disease progression in CRZ-treated ALK+ NSCLC. The ALTA trial is assessing BRG, an investigational next-generation ALK inhibitor, in pts with CRZ-refractory advanced ALK+ NSCLC, including pts with baseline brain metastases. Methods: In ALTA (NCT02094573), pts were stratified by presence of baseline brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Here, we show data for pts with baseline brain metastases. An independent review committee (IRC) assessed intracranial efficacy. Results: Of 222 pts (112 in arm A; 110 in arm B), 80 (71%)/74 (67%) in A/B had baseline brain metastases per investigators, with median age 49/55 y; 74%/76% had received chemotherapy. As of May 31, 2016, 51%/59% of these pts continued to receive BRG in A/B; median follow-up was 9.6/11.4 mo. Intracranial efficacy is shown in the table. Among these pts, most common treatment-emergent adverse events were: nausea 35%/46% (A/B), headache 30%/31%, vomiting 29%/31%, diarrhea 21%/38%, cough 25%/32%; grade ≥3: increased blood CPK 1%/12%, hypertension 4%/7%, increased lipase 4%/3%. Conclusions: BRG yielded substantial intracranial responses with robust iPFS and acceptable safety in ALK+ NSCLC pts with baseline brain metastases in ALTA. 180 mg (with lead-in) showed consistently improved intracranial efficacy compared with 90 mg. Clinical trial information: NCT02094573. [Table: see text]
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Burgos, José, Aitor Viribay, Diego Fernández-Lázaro, Julio Calleja-González, Josefa González-Santos, and Juan Mielgo-Ayuso. "Combined Effects of Citrulline Plus Nitrate-Rich Beetroot Extract Co-Supplementation on Maximal and Endurance-Strength and Aerobic Power in Trained Male Triathletes: A Randomized Double-Blind, Placebo-Controlled Trial." Nutrients 14, no. 1 (December 23, 2021): 40. http://dx.doi.org/10.3390/nu14010040.

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Citrulline (CIT) and nitrate-rich beetroot extract (BR) are ergogenic aids and nitric oxide (NO) precursors. In addition, both supplements seem to have other actions at the level of muscle metabolism that can benefit strength and aerobic power performance. Both supplements have been studied in numerous investigations in isolation. However, scientific evidence combining both supplements is scarce, and to the best of the authors’ knowledge, there is no current study of endurance athletes. Therefore, the main purpose of this study was to determine the effect of 9 weeks of CIT plus BR supplementation on maximal and endurance-strength performance and aerobic power in male triathletes. This study was a randomized double-blind, placebo-controlled trial where participants (n = 32) were randomized into four different groups: placebo group (PLG; n = 8), CIT plus BR group (CIT- BRG; 3 g/kg/day of CIT plus 3 mg/kg/day of nitrates (NO3−); n = 8), CIT group (CITG; 3 g/kg/day; n = 8) and BR group (BRG; 3 mg/kg/day of NO3−; n = 8). Before (T1) and after 9 weeks (T2), four physical condition tests were carried out in order to assess sport performance: the horizontal jump test (HJUMP), handgrip dynamometer test, 1-min abdominal tests (1-MAT) and finally, the Cooper test. Although, no significant interactions (time × supplementation groups) were found for the strength tests (p > 0.05), the CIT- BRG supplementation presented a trend on HJUMP and 1-MAT tests confirmed by significant increase between two study moments in CIT-BRG. Likewise, CIT-BRG presented significant interactions in the aerobic power test confirmed by this group’s improve estimated VO2max during the study with respect to the other study groups (p = 0.002; η2p = 0.418). In summary, supplementing with 3 g/day of CIT and 2.1 g/day of BR (300 mg/day of NO3−) for 9 weeks could increase maximal and endurance strength. Furthermore, when compared to CIT or BR supplementation alone, this combination improved performance in tests related to aerobic power.
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Strobeck, Matthew W., Marc F. DeCristofaro, Fatima Banine, Bernard E. Weissman, Larry S. Sherman, and Erik S. Knudsen. "The BRG-1 Subunit of the SWI/SNF Complex Regulates CD44 Expression." Journal of Biological Chemistry 276, no. 12 (December 6, 2000): 9273–78. http://dx.doi.org/10.1074/jbc.m009747200.

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29

Phan, Thuy Thi, Trung Quoc Nguyen, and Huong Thi Do. "Agronomic Characteristics, Anthocyanin Content, and Antioxidant Activity of Anthocynins Extracted from the Seeds of Black Rice Accessions." Vietnam Journal of Agricultural Sciences 1, no. 3 (February 13, 2019): 208–19. http://dx.doi.org/10.31817/vjas.2018.1.3.02.

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The objectives of this study were to investigate the morphological characteristics, grain yield, and anthocyanin content of 36 black rice accessions that were collected from different locations in Vietnam. The results showed that the black rice accessions varied in growth duration (130 to 150 days), plant height (91.5 to 143.6 cm), morphological characteristics, and yield components. Grain yield of the black rice accessions ranged from 2.8 to 8.7 tons ha-1. The black rice accessions were classified into four groups based on their anthocyanin content: group I > 0.1% anthocyanin, group II 0.05%-0.1%, group III 0.001%-0.05%, and group IV < 0.001%. BR7 had the highest anthocyanin content (0.1438%), followed by BR5 (0.1317%). Anthocyanins with the strongest antioxidant activities were extracted from BR8, BR35, BR6, BR27, BR30, BR32, BR18, BR17, BR19, and BR1 with IC50 values less than 2 µg mL-1. Seven promising black rice accessions, namely BR1, BR14, BR17, BR25, BR30, BR34, and BR35, were selected for further research based on their high anthocyanin contents, and good grain yield and yield components.
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Patel, Amir, Mart DelaCruz, Ramesh Wali, Dhananjay Kunte, and Hemant Roy. "Towards Understanding Chemoprevention of Colon Carcinogenesis: Role of Epigenetic Modulation of Brahma-Related Gene 1 (BRG-1)." American Journal of Gastroenterology 107 (October 2012): S808—S809. http://dx.doi.org/10.14309/00000434-201210001-01982.

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31

Hilz, Max J., Sankanika Roy, Carmen de Rojas Leal, Mao Liu, Francesca Canavese, Klemens Winder, Katharina M. Hoesl, De-Hyung Lee, Ralf A. Linker, and Ruihao Wang. "Cardiovascular fingolimod effects on rapid baroreceptor unloading are counterbalanced by baroreflex resetting." Neurological Sciences 42, no. 1 (January 2021): 111–21. http://dx.doi.org/10.1007/s10072-020-05004-1.

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Abstract Background and purpose Initial cardiovascular fingolimod effects might compromise baroreflex responses to rapid blood pressure (BP) changes during common Valsalva-like maneuvers. This study evaluated cardiovascular responses to Valsalva maneuver (VM)-induced baroreceptor unloading and loading upon fingolimod initiation. Patients and methods Twenty-one patients with relapsing-remitting multiple sclerosis performed VMs before and 0.5, 1, 2, 3, 4, 5, and 6 hours after fingolimod initiation. We recorded heart rate (HR) as RR intervals (RRI), systolic and diastolic BP (BPsys, BPdia) during VM phase 1, VM phase 2 early, VM phase 2 late, and VM phase 4. Using linear regression analysis between decreasing BPsys and RRI values during VM phase 2 early, we determined baroreflex gain (BRG) reflecting vagal withdrawal and sympathetic activation upon baroreceptor unloading. To assess cardiovagal activation upon baroreceptor loading, we calculated Valsalva ratios (VR) between maximal and minimal RRIs after strain release. Analysis of variance or Friedman tests with post hoc analysis compared corresponding parameters at the eight time points (significance: p < 0.05). Results RRIs at VM phase 1, VM phase 2 early, and VM phase 2 late were higher after than before fingolimod initiation, and maximal after 4 hours. Fingolimod did not affect the longest RRIs upon strain release, but after 3, 5, and 6 hours lowered the highest BPsys values during overshoot and all BPdia values, and thus reduced VRs. BRG was slightly higher after 3 and 5 hours, and significantly higher after 4 hours than before fingolimod initiation. Conclusions VR-decreases 3–6 hours after fingolimod initiation are physiologic results of fingolimod-associated attenuations of BP and HR increases at the end of strain and do not suggest impaired cardiovagal activation upon baroreceptor loading. Stable and at the time of HR nadir significantly increased BRGs indicate improved responses to baroreceptor unloading. Thus, cardiovascular fingolimod effects do not impair autonomic responses to sudden baroreceptor loading or unloading but seem to be mitigated by baroreflex resetting.
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Tourigny, Ghislain, Claude Hubert, A. C. Brown, and Robert Crépeau. "Structural geology of the Blake River Group at the Bousquet mine, Abitibi, Quebec." Canadian Journal of Earth Sciences 25, no. 4 (April 1, 1988): 581–92. http://dx.doi.org/10.1139/e88-056.

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In the Bousquet mining district, metamorphosed volcanic rocks of the Blake River Group (BRG) exhibit discrete strain features resulting from three generations of structures—D1, D2, and D3. Deformation D1 formed an east–west-trending, subvertical, penetrative schistosity that is coplanar with the axial plane of associated folds. This foliation contains a linear fabric plunging steeply westward, and mineral lineations are subparallel to fold axes and to intersection lineations.Defomations D2 and D3 formed a crenulation cleavage and a set of conjugate kink bands, respectively. The cleavage is oriented east–northeast, and the kink bands are oriented northeast–southwest and northwest–southeast. Both deformations distorted earlier-formed structures to a minor extent. A conjugate set of minor strike-slip faults with orientations similar to the kinks are the youngest structures found in BRG rocks.The volcanic sequence is composed of two lithotectonic domains juxtaposed along fault-related contacts. Each domain exhibits distinctive strain features attributed mainly to a broad network of anastomosing faults. This network of faults disrupted strata and destroyed many internal stratigraphic features, especially in domain 2; it relates to late stages of D1.Domain 1, occupying the northern half of the BRG in the mine area, represents a zone of weakly sheared tholeiitic basalts 750 m thick and is overlain by 150 m of felsic volcaniclastic rocks. Primary textures and structures indicate that this domain forms a south-facing homoclinal succession.Domain 2 is characterized by a strongly strained, 500 m wide belt of anastomosing faults adjacent to the southern margin of domain 1. Narrow bands of schist, mylonite, and phyllonite straddle fault zones and surround less-deformed, lozenge-shaped blocks of metamorphosed volcanic and (or) volcaniclastic rocks.The lack of syngenetic structures and textures, together with intense faulting and transposition, restricts stratigraphic correlations throughout the BRG as well as correlations between this volcanic succession and the adjacent sedimentary units. Structural evidence presented here complicates the original stratigraphic scheme commonly applied to volcano-sedimentary assemblages in the Rouyn–Val D'Or area. It is proposed that faulting is responsible for the spatial distribution of lithologies previously interpreted as resulting from folding phenomena in the Bousquet mining district. Gold mineralization is concentrated in bands of deformed rocks in the fault zones of domain 2 at the Bousquet mine.
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Bourachot, Brigitte, Moshe Yaniv, and Christian Muchardt. "The Activity of Mammalian brm/SNF2α Is Dependent on a High-Mobility-Group Protein I/Y-Like DNA Binding Domain." Molecular and Cellular Biology 19, no. 6 (June 1, 1999): 3931–39. http://dx.doi.org/10.1128/mcb.19.6.3931.

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ABSTRACT The mammalian SWI-SNF complex is a chromatin-remodelling machinery involved in the modulation of gene expression. Its activity relies on two closely related ATPases known as brm/SNF2α and BRG-1/SNF2β. These two proteins can cooperate with nuclear receptors for transcriptional activation. In addition, they are involved in the control of cell proliferation, most probably by facilitating p105Rb repression of E2F transcriptional activity. In the present study, we have examined the ability of various brm/SNF2α deletion mutants to reverse the transformed phenotype ofras-transformed fibroblasts. Deletions within the p105Rb LXCXE binding motif or the conserved bromodomain had only a moderate effect. On the other hand, a 49-amino-acid segment, rich in lysines and arginines and located immediately downstream of the p105Rb interaction domain, appeared to be essential in this assay. This region was also required for cooperation of brm/SNF2α with the glucocorticoid receptor in transfection experiments, but only in the context of a reporter construct integrated in the cellular genome. The region has homology to the AT hooks present in high-mobility-group protein I/Y DNA binding domains and is required for the tethering of brm/SNF2α to chromatin.
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Yang, Chuanhe, Yinan Wang, Michelle M. Sims, Yali He, Duane D. Miller, and Lawrence M. Pfeffer. "Targeting the Bromodomain of BRG-1/BRM Subunit of the SWI/SNF Complex Increases the Anticancer Activity of Temozolomide in Glioblastoma." Pharmaceuticals 14, no. 9 (September 6, 2021): 904. http://dx.doi.org/10.3390/ph14090904.

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Glioblastoma (GBM) is a deadly and incurable brain cancer with limited therapeutic options. PFI-3 is a small-molecule bromodomain (BRD) inhibitor of the BRM/BRG1 subunits of the SWI/SNF chromatin remodeling complex. The objective of this study is to determine the efficacy of PFI-3 as a potential GBM therapy. We report that PFI-3 binds to these BRDs when expressed in GBM cells. PFI-3 markedly enhanced the antiproliferative and cell death-inducing effects of temozolomide (TMZ) in TMZ-sensitive GBM cells as well as overcame the chemoresistance of highly TMZ-resistant GBM cells. PFI-3 also altered gene expression in GBM and enhanced the basal and interferon-induced expression of a subset of interferon-responsive genes. Besides the effects of PFI-3 on GBM cells in vitro, we found that PFI-3 markedly potentiated the anticancer effect of TMZ in an intracranial GBM animal model, resulting in a marked increase in survival of animals bearing GBM tumors. Taken together, we identified the BRG1 and BRM subunits of SWI/SNF as novel targets in GBM and revealed the therapeutic potential of applying small molecule inhibitors of SWI/SNF to improve the clinical outcome in GBM using standard-of-care chemotherapy.
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Nacht, Ana Silvina, Andy Pohl, Roser Zaurin, Daniel Soronellas, Javier Quilez, Priyanka Sharma, Roni H. Wright, Miguel Beato, and Guillermo P. Vicent. "Hormone‐induced repression of genes requires BRG 1‐mediated H1.2 deposition at target promoters." EMBO Journal 35, no. 16 (July 7, 2016): 1822–43. http://dx.doi.org/10.15252/embj.201593260.

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Kuo, Kuan-Ting, Cher-Wei Liang, Chen-Hsiang Hsiao, Ching-Hung Lin, Chi-An Chen, Bor-Ching Sheu, and Ming-Chieh Lin. "Downregulation of BRG-1 repressed expression of CD44s in cervical neuroendocrine carcinoma and adenocarcinoma." Modern Pathology 19, no. 12 (September 22, 2006): 1570–77. http://dx.doi.org/10.1038/modpathol.3800687.

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37

Wang, G., Y. Fu, X. Yang, X. Luo, J. Wang, J. Gong, and J. Hu. "Brg-1 targeting of novel miR550a-5p/RNF43/Wnt signaling axis regulates colorectal cancer metastasis." Oncogene 35, no. 5 (May 11, 2015): 651–61. http://dx.doi.org/10.1038/onc.2015.124.

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38

Barker, N. "The chromatin remodelling factor Brg-1 interacts with beta-catenin to promote target gene activation." EMBO Journal 20, no. 17 (September 3, 2001): 4935–43. http://dx.doi.org/10.1093/emboj/20.17.4935.

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39

Tanapant, Samustpon. "Book Review: Beyond Bending: Reimaging Compression Shells." Journal of Architectural/Planning Research and Studies (JARS) 16, no. 1 (June 26, 2019): 139–44. http://dx.doi.org/10.56261/jars.v16i1.192576.

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สาระในหนังสือเล่มนี้คือสัมฤทธิ์ผลที่เกิดจากการศึกษาภายใต้กรอบแนวคิดการวิจัย (Research framework) 5 ประเด็น คือ 1) การวิเคราะห์โครงสร้างที่เกิดจากการก่อ (Analysis of masonry structure) 2) การศึกษาการออกแบบและพัฒนาโครงสร้างด้วยแผนภาพแรง (Graphical analysis and design methods) 3) การใช้ระเบียบวิธีเชิงคอมพิวเทชั่นในการค้นหารูปทรงของโครงสร้างที่เหมาะสม (Computational form finding and optimization) 4) การออกแบบเพื่อการประกอบแบบไร้วัสดุประสาน (Design of discrete assemblies) และ 5) ระบบการผลิตและก่อสร้างด้วยเทคโนโลยีดิจิทัลแฟบริคเคชั่น (Digital fabrication) โดยกลุ่มวิจัยบล็อก (The Block Research Group : BRG) สถาบันเทคโนโลยีแห่งสหพันธ์สวิสในซูริก ภายใต้การนำของศาสตราจารย์ ด็อกเตอร์ ฟิลิป บล็อก และ ด็อกเตอร์ ทอม เวน เมล หนังสือเล่มนี้แบ่งเนื้อหาออกเป็น 2 ส่วนตามสาระที่ถูกจัดแสดงในนิทรรศการสถาปัตยกรรมนานาชาติ เวนิสเบียนาเล่ พ.ศ. 2559 (La Biennale di Venezia, the 15th International Architecture Exhibition in 2016) ซึ่งประกอบด้วย 1) Beyond Bendingและ 2) The Making of the Armadillo Vault เนื้อหาทั้ง 2 ส่วนนี้ไม่เพียงนำเสนอฐานความรู้เชิงทฤษฎีและกรณีศึกษาต่าง ๆ ของกลุ่มวิจัยบล็อกเท่านั้นแต่ยังนำเสนอความรู้เชิงเทคนิค ระเบียบขั้นตอนการออกแบบ การผลิต การประกอบ และก่อสร้างทุกขั้นตอนตลอดจนไปถึงการรื้อถอนโดยละเอียด
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40

Wang, G., Y. Fu, X. Yang, X. Luo, J. Wang, J. Gong, and J. Hu. "Erratum: Brg-1 targeting of novel miR550a-5p/RNF43/Wnt signaling axis regulates colorectal cancer metastasis." Oncogene 36, no. 42 (August 28, 2017): 5915. http://dx.doi.org/10.1038/onc.2017.317.

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41

Milants, Christophe, Olivier Bruyère, and Jean-François Kaux. "Responders to Platelet-Rich Plasma in Osteoarthritis: A Technical Analysis." BioMed Research International 2017 (2017): 1–11. http://dx.doi.org/10.1155/2017/7538604.

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Purpose.To evaluate the similarities and differences between the variety of platelet-rich plasma (PRP) formulations, preparation, and uses to try to determine the best responses for the treatment of knee osteoarthritis.Materials and Methods.A comparison of the outcomes of randomized controlled trials (RCTs) included in the 3 most recent and high-quality meta-analyses to classify the different studies in 2 groups (bad responders group (BRG) and very good responders group (VGRG)).Results and Discussion.From the 19 RCTs analyzed, 7 trials were included in the VGRG and 4 in the BRG. In VGRG, 1 or 2 injections were performed in 4/7 trials, time between injections was 2 to 3 weeks in 4/5 studies with many injections, volume injected varied from 2.5 to 8 mL, and single spinning technique was used in 5/7 studies. PRP classification was Mishra 4B and PAWP2Bβin 5/7 studies. The use of PRP with leukocytes is only found in the BRG.Conclusion.There is a lack of standardization in PRP preparation technique for knee osteoarthritis. However it appears that the use of a single spinning technique, a platelet concentration lower than 5 times the baseline, and avoidance of leukocytes should be preferred.
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42

Torres-Padilla, Maria Elena, and Magdalena Zernicka-Goetz. "Role of TIF1α as a modulator of embryonic transcription in the mouse zygote." Journal of Cell Biology 174, no. 3 (July 31, 2006): 329–38. http://dx.doi.org/10.1083/jcb.200603146.

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The first events of the development of any embryo are under maternal control until the zygotic genome becomes activated. In the mouse embryo, the major wave of transcription activation occurs at the 2-cell stage, but transcription starts already at the zygote (1-cell) stage. Very little is known about the molecules involved in this process. We show that the transcription intermediary factor 1 α (TIF1α) is involved in modulating gene expression during the first wave of transcription activation. At the onset of genome activation, TIF1α translocates from the cytoplasm into the pronuclei to sites of active transcription. These sites are enriched with the chromatin remodelers BRG-1 and SNF2H. When we ablate TIF1α through either RNA interference (RNAi) or microinjection of specific antibodies into zygotes, most of the embryos arrest their development at the 2–4-cell stage transition. The ablation of TIF1α leads to mislocalization of RNA polymerase II and the chromatin remodelers SNF2H and BRG-1. Using a chromatin immunoprecipitation cloning approach, we identify genes that are regulated by TIF1α in the zygote and find that transcription of these genes is misregulated upon TIF1α ablation. We further show that the expression of some of these genes is dependent on SNF2H and that RNAi for SNF2H compromises development, suggesting that TIF1α mediates activation of gene expression in the zygote via SNF2H. These studies indicate that TIF1α is a factor that modulates the expression of a set of genes during the first wave of genome activation in the mouse embryo.
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43

Адонин, С. А. "Кристаллические структуры полибромидных солей бис(пиридил)алкан-дикатионов." Журнал структурной химии 62, no. 7 (2021): 1116–20. http://dx.doi.org/10.26902/jsc_id76135.

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Реакции растворов 1,1'-(алкан-1,х-диил)-бис(пиридиний) дибромидов ((PyCx)Br2) с 1M Br2 в HBr ведут к образованию трибромидов (PyCx)(Br3)2 (x = 3 (1), 4 (2), 5 (3)) и пентабромида (PyC6)(Br5)2 (4) соответственно, строение которых изучено методом РСА. В структуре 4 присутствуют нековалентные взаимодействия Br⋯Br, связывающие анионы Br5– в двухмерные супрамолекулярные ассоциаты.
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44

Tai, K.-Y., Y.-S. Shieh, C.-S. Lee, S.-G. Shiah, and C.-W. Wu. "Axl promotes cell invasion by inducing MMP-9 activity through activation of NF-κB and Brg-1." Oncogene 27, no. 29 (March 17, 2008): 4044–55. http://dx.doi.org/10.1038/onc.2008.57.

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45

Habermehl, Katja, and Gerd Meyer. "Triniobiumoctabromide, Nb3Br8, Revisited." Zeitschrift für Naturforschung B 65, no. 6 (June 1, 2010): 770–72. http://dx.doi.org/10.1515/znb-2010-0615.

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A facile route to single crystals of Nb3Br8 by the reaction of NbBr5 with the wall of the niobium reaction vessel at 800 °C is reported. The crystal structure (a = 707.87(5), c = 3895.7(6) pm, R3̄m, Z = 6) was determined from diffractometer data; the crystal data are compared with those obtained from film data in 1966 which were of already high precision. Triangular {Nb3} clusters with Nb-Nb distances of 288.6(2) pm are surrounded by 13 bromide ligands which bridge them to double layers, {Nb3}(μ3-Br4)i1/1(μ2- Br1)i(3/2)・2(μ1-Br2)a-a 6/2(μ1-Br3)a-a-a3/3 that are stacked to a 12R structure.
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46

Hartati, Fadjar Kurnia, and Andryanto A. "Black Rice Extract Induced Apoptosis and Cell Cycle Arrest on Human Cancer Cell Lines." Current Research in Nutrition and Food Science Journal 10, no. 3 (December 20, 2022): 971–79. http://dx.doi.org/10.12944/crnfsj.10.3.14.

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The purpose of the research is to evaluate the anti-cancer outcomes of aqueous black rice (BR) extract on human cancer cell lines; HeLa, T47D, and U2OS. To begin the investigation, the total phenol and flavonoid content of the BR extract was determined. Additionally, the antioxidant activity of the extract was determined using the ferric reducing antioxidant power (FRAP), total antioxidant capacity (TAC), and 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) assays. The cell viability, apoptosis and cell cycle on several human cancer cells were determined after BR extract administration in several doses (BR1; 100 mg/ml, BR2; 200 mg/ml, BR3; 300 mg/ml, BR4; 400 mg/ml, and BR5; 500 mg/ml) using flow cytometry analysis. According to the analysis, the extract had total phenol and flavonoid content are 66.42 mg/g and 11.12 mg/g, respectively. Based on the assay of DPPH (53.19 µg/ml), FRAP (49.86 mg/g), and TAC (96.70 mg/g), BR extract showed strong antioxidant activity. This study also revealed that BR extract significantly reduced human cancer cell lines viability and selectively (shown to have no effect on PBMC cells) (p<0.05) especially BR5 group (500 g/mL) . The administration of BR extract was most responsive to induce apoptosis in T47D cells, up to 93.64 % in BR5 close to cisplatin-induced apoptosis effect, compared to HeLa and U2OS cells. The study also found BR extract induced the cell (HeLa, T47D, and U2OS) to arrest or in the phase G0/G1. Hence, BR extract was a food-based cancer treatment with a promising effect to inhibit cancer cell growth and progression.
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47

TARASOV, V. F. "ON EXACT HYPERGEOMETRIC SOLUTIONS OF CERTAIN SOLITON-LIKE EQUATIONS." International Journal of Modern Physics B 24, no. 23 (September 20, 2010): 4509–19. http://dx.doi.org/10.1142/s0217979210056645.

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It is shown that certain nonlinear wave evolution equations in (1+1)-dimensional space-time in the soliton theory: sine-Gordon (SG), sinh-Gordon (ShG), the nonlinear Schrödinger equation (NLS), the φ4 equation in quantum field theory, the Burgers diffusion equation (Brg) and the Huxley equation (Hsl) in biophysics, the Boussinesq equation (Bsq), can be solved in terms of hypergeometric functions of pFq-type. Such approach allows to establish the connection between "model" equations and simple functional relations (in the form of diagrams) of these functions; the latter gives the possibility to consider a number of "inverse problems" in the soliton theory in a new way and to get new "models" of solitary waves.
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48

Langer, Corey J., Hui Huang, Joice Huang, David Kerstein, William Reichmann, Rebecca M. Speck, and William R. Lenderking. "Patient-reported outcomes and quality of life in ALTA: The randomized phase 2 study of brigatinib (BRG) in advanced ALK+ non–small cell lung cancer (NSCLC)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 9066. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.9066.

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9066 Background: The ALTA trial (NCT02094573), an open-label, phase 2, randomized, multicenter, international study, evaluated the efficacy and safety of BRG (arm A: 90 mg qd and arm B: 180 mg qd with 7-day lead-in at 90 mg) in patients (pts) with advanced anaplastic lymphoma kinase–positive (ALK+) NSCLC whose disease had progressed on prior therapy with crizotinib (CRZ). The objective of this analysis was to describe pt-reported outcomes (PROs) in the ALTA study. Methods: PROs were collected using the EORTC QLQ-C30 at baseline and on the first day of each cycle. Multivariable mixed effects models were constructed to estimate adjusted mean changes from baseline in QLQ-C30 scores. Cumulative distribution function (CDF) plots of EORTC QLQ-C30 change scores from baseline to Cycle 5 were generated to evaluate a clinically meaningful threshold of individual pt change, which was determined through anchor- and distribution-based methods. Results: Among 222 randomized pts, 208 (94%) completed the questionnaire at baseline and at least 1 on-treatment PRO follow-up. In multivariable analyses, there were no statistically significant differences in Global Health Status (GHS)/QOL between arms over time when adjusted for baseline score, ECOG status, and presence of liver or bone metastases. At Cycle 5, CDF plots indicated that 80% of all pts experienced an increase or no change in GHS/QOL scores; 50% of all pts experienced a clinically meaningful improvement. At Cycle 5, 80% of all pts reported a reduction or no change in pain score, and 90% of all pts reported a reduction or no change in dyspnea score. Approximately 30% of pts had clinically meaningful reductions in these symptoms. Less than 15% and < 5% of all pts reported clinically meaningful worsening of nausea/vomiting and diarrhea scores, respectively, at Cycle 5. Conclusions: Treatment with BRG for CRZ-refractory ALK+ NSCLC resulted in improved GHS/QOL scores and reduction in pain and dyspnea scores, while rates for nausea/vomiting and diarrhea were minimally worse. These pt-level benefits support BRG as a promising treatment option. Clinical trial information: NCT02094573.
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Hönle, Wolfgang, Sigrid Furuseth, and Hans Georg von Schnering. "Synthesis and Crystal Structure of Ordered, Orthorhombic α-NbBr5." Zeitschrift für Naturforschung B 45, no. 7 (July 1, 1990): 952–56. http://dx.doi.org/10.1515/znb-1990-0706.

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Niobium pentabromide, NbBr5, is prepared in the orthorhombic ordered (α)-form from the elements in sealed quartz ampoules (Nb powder, Br2, l) at 973 K. The structure has been determined from single crystal data (a = 1288.8(2), b = 1869.0(3), c = 614.9(1) pm; Pnma (No. 62); Z = 8; R = 0.055). α-NbBr5_ forms dimeric Nb2Br10 molecules with d̄(Nb–Brb) = 271.5 pm, d̄(Nb–Bre) = 240.8 pm and d̄(Nb– Bra) = 246.1 pm. α-NbBr5 is a diamagnetic semiconductor with cgsχmoldia(300 K) = –72 × 10-6 cm3/mol. The band gaps of NbCl5, α-NbBr5 and NbI5 have been determined by diffuse reflection to be Eg(NbCl5) = 2.74 eV, Eg(α-NbBr5) = 1.99 eV, and Eg(NbI5) = 0.99 eV.
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Afifah, Rohima Sera. "FALLING HEAD (FH) UNTUK HUBUNGAN SIFAT BATUAN DENGAN KOEFISIEN KELULUSAN AIR DI DAERAH “BRG” SEKITARNYA." AL-ULUM: JURNAL SAINS DAN TEKNOLOGI 8, no. 1 (November 5, 2022): 30. http://dx.doi.org/10.31602/ajst.v8i1.8918.

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The basalt of "Ohi" Mount and the Andesite Hornblend on "Ser" Mount are a barrier to the flow of groundwater from "Ifa" Mount. Both are an influence on the productivity aquifer. The characteristic of lithology in water is an influence of the permeability coefficient. Falling head is one of the methods of measuring the determination of coefficient permeability. Based on the location measurement, To know the units of rock formed, (2) To know the Productivity aquifer system (local, medium and small); (3) To know the coefficient permeability of characteristics of lithology. Coefficient of Permeability A stream is said to be good if the nature of the rock type has a positive result or the greater the water pass rate, and conversely, the passing value of a negative result has a very small water pass rate. Its goal was to determine the relationship between lithology characteristics and permeability coefficients in the "BRG" area and surroundings. The "BRG" area and its surroundings, based on the location point of measurement of the rock unit, were the Breccia Andesite Hornblend unit, The Medium Productivity Aquifer Dominated. The average coefficient of permeability (K) is 63,300 cm/day. The five location measurements were: 1 st area DS, S1, 2 nd DS area, S2, 3 rd DN area, 4 th DD area, and 5 th DR. The aquifer of the five locations had through fracture permeability and had a type of steep hill morphology
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