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HORIKOSHI, Takashi. "BRM therapy." Skin Cancer 8, no. 1 (1993): 43–50. http://dx.doi.org/10.5227/skincancer.8.43.
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Thompson, Kenneth W., Stefanie B. Marquez, Li Lu, and David Reisman. "Induction of functional Brm protein from Brm knockout mice." Oncoscience 2, no. 4 (April 18, 2015): 349–61. http://dx.doi.org/10.18632/oncoscience.153.
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Kataoka, Kazunori. "Biological Response Modifier (BRM)." Kobunshi 41, no. 10 (1992): 722a. http://dx.doi.org/10.1295/kobunshi.41.722a.
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Liu, Zhao-Yang, Ze-guang Wang, Wei Zhang, Hai-mei Tian, Hui Li, Di-ya Na, Dong-yan Cao, Yi Liu, and Mo Li. "Antitumor effect of BRM." Chinese Journal of Cancer Research 14, no. 3 (September 2002): 195–201. http://dx.doi.org/10.1007/s11670-002-0044-1.
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Fischer, Marcus, Florian Imgrund, Christian Janiesch, and Axel Winkelmann. "Directions for future research on the integration of SOA, BPM, and BRM." Business Process Management Journal 25, no. 7 (October 14, 2019): 1491–519. http://dx.doi.org/10.1108/bpmj-05-2018-0130.
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Purpose Digital transformation has been changing the economic environment of enterprises in recent years. To remain competitive, they rely on an extensible software architecture, flexible workflow execution, and automated decision management. The concepts of service-oriented architectures (SOA), business process management (BPM), and business rules management (BRM) provide an adequate, yet isolated means of addressing many of these requirements. The paper aims to discuss these issues. Design/methodology/approach This study adapts from established research frameworks to structure the current state of research on the integration of SOA, BPM and BRM. The authors highlight the current research scope, point to disregarded topics and sketch out multidisciplinary research approaches. Findings While the three concepts are often discussed only in isolation or pairwise, approaches that integrate them are scarce. Against this backdrop, this study defines three types of research opportunities and identifies several directions for future research that should be explored from a technological as well as organizational perspective. Given the breadth of open questions, the authors present sources for each area of our research framework, which can serve as starting points for future investigations. Practical implications Except for well-established support for separate tasks and technologies, there is a lack of integrated standards, methods and platforms, which for example enable integrated decision-making across BPM and SOA. Originality/value Our contribution builds on established frameworks and clearly shows that the discussion on the integration of SOA, BPM and BRM cannot yet be regarded as sufficient. The research agenda highlights which areas explicitly benefit from a more precise consideration.
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Ou, Yang, Zheng Jiang Liu, Hamid Reza Karimi, and Ying Tian. "Multilevel Association Rule Mining for Bridge Resource Management Based on Immune Genetic Algorithm." Abstract and Applied Analysis 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/278694.
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This paper is concerned with the problem of multilevel association rule mining for bridge resource management (BRM) which is announced by IMO in 2010. The goal of this paper is to mine the association rules among the items of BRM and the vessel accidents. However, due to the indirect data that can be collected, which seems useless for the analysis of the relationship between items of BIM and the accidents, the cross level association rules need to be studied, which builds the relation between the indirect data and items of BRM. In this paper, firstly, a cross level coding scheme for mining the multilevel association rules is proposed. Secondly, we execute the immune genetic algorithm with the coding scheme for analyzing BRM. Thirdly, based on the basic maritime investigation reports, some important association rules of the items of BRM are mined and studied. Finally, according to the results of the analysis, we provide the suggestions for the work of seafarer training, assessment, and management.
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MARTINS, BÁRBARA ESTEVAM DE MELO, AMANDA ABDALLAH CHAIBUB, MARCIO VINICIUS DE CARVALHO BARROS CORTÊS, VALÁCIA LEMES DA SILVA LOBO, and MARTA CRISTINA CORSI DE FILIPPI. "CHARACTERIZATION OF BACTERIAL ISOLATES FOR SUSTAINABLE RICE BLAST CONTROL." Revista Caatinga 33, no. 3 (September 2020): 702–12. http://dx.doi.org/10.1590/1983-21252020v33n313rc.
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ABSTRACT Rice blast (Magnaporthe oryzae) limits rice (Oryza sativa) grain yields worldwide. The objective of this investigation was to morphologically, biochemically, and molecularly characterize six bacterial isolates, BRM 32109, BRM 32110, BRM 32111, BRM 32112, BRM 32113, and BRM 32114, and to determine their potential as antagonists to M. oryzae. Morphological characterization was based on colony formation and color, Gram staining, and fluorescent pigment production. Biochemical studies were based on cellulase, chitinase, phosphatase, indoleacetic acid, and siderophore production, as well as biofilm formation. The molecular identification used specific primers for PCR amplification of the 16S rRNA region, followed by sequencing. The antagonism studies involved three experiments, which had randomized designs. Two of them were conducted in laboratory conditions, pairing bacterial colonies and M. oryzae, using bacterial filtrates, and the third was conducted in greenhouse conditions. BRM 32111 and BRM 32112 were identified as Pseudomonas sp., BRM 32113 as Burkholderia sp., BRM 32114 as Serratia sp., and BRM 32110 and BRM 32109 as Bacillus spp. BRM 32112, BRM 32111, and BRM 32113 inhibited the colony of M. oryzae by 68%, 65%, and 48%, respectively. The bacterial suspensions of the BRM 32111, BRM 32112, and BRM 3212 filtrates suppressed leaf blast by 81.0, 79.2, and 66.3%, respectively. BRM 32111 and BRM 32112 were determined to be antagonists of M. oryzae and were found to solubilize phosphate, produce siderophores and cellulose, form biofilms, and suppress leaf blast. These isolates should be further investigated as potential biological control agents for leaf blast control.
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Park, Song Yi, Sang-Hwa Lee, Min-Jeong Kim, Ki-Hwan Ji, and Ji Ho Ryu. "Comparing the cut score for the borderline group method and borderline regression method with norm-referenced standard setting in an objective structured clinical examination in medical school in Korea." Journal of Educational Evaluation for Health Professions 18 (September 27, 2021): 25. http://dx.doi.org/10.3352/jeehp.2021.18.25.
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Purpose: Setting standards is critical in health professions. However, appropriate standard setting methods do not always apply to the set cut score in performance assessment. The aim of this study was to compare the cut score when the standard setting is changed from the norm-referenced method to the borderline group method (BGM) and borderline regression method (BRM) in an objective structured clinical examination (OSCE) in medical school.Methods: This was an explorative study to model of the BGM and BRM. A total of 107 fourth-year medical students attended the OSCE at seven stations with encountering standardized patients (SPs) and one station with performing skills on a manikin on 15 July 2021. Thirty-two physician examiners evaluated the performance by completing a checklist and global rating scales.Results: The cut score of the norm-referenced method was lower than that of the BGM (p<0.01) and BRM (p<0.02). There was no significant difference in the cut score between the BGM and BRM (p=0.40). The station with the highest standard deviation and the highest proportion of the borderline group showed the largest cut score difference in standard setting methods.Conclusion: Prefixed cut scores by the norm-referenced method without considering station contents or examinee performance can vary due to station difficulty and content, affecting the appropriateness of standard setting decisions. If there is an adequate consensus on the criteria for the borderline group, standard setting with the BRM could be applied as a practical and defensible method to determine the cut score for OSCE.
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Elfring, Lisa K., Carla Daniel, Ophelia Papoulas, Renate Deuring, Melinda Sarte, Sarah Moseley, Shelley J. Beek, et al. "Genetic Analysis of brahma: The Drosophila Homolog of the Yeast Chromatin Remodeling Factor SWI2/SNF2." Genetics 148, no. 1 (January 1, 1998): 251–65. http://dx.doi.org/10.1093/genetics/148.1.251.
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Abstract The Drosophila brahma (brm) gene encodes an activator of homeotic genes related to the yeast chromatin remodeling factor SWI2/SNF2. Here, we report the phenotype of null and dominant-negative brm mutations. Using mosaic analysis, we found that the complete loss of brm function decreases cell viability and causes defects in the peripheral nervous system of the adult. A dominant-negative brm mutation was generated by replacing a conserved lysine in the ATP-binding site of the BRM protein with an arginine. This mutation eliminates brm function in vivo but does not affect assembly of the 2-MD BRM complex. Expression of the dominant-negative BRM protein caused peripheral nervous system defects, homeotic transformations, and decreased viability. Consistent with these findings, the BRM protein is expressed at relatively high levels in nuclei throughout the developing organism. Site-directed mutagenesis was used to investigate the functions of conserved regions of the BRM protein. Domain II is essential for brm function and is required for the assembly or stability of the BRM complex. In spite of its conservation in numerous eukaryotic regulatory proteins, the deletion of the bromodomain of the BRM protein has no discernible phenotype.
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Akash, D., N. Earanna, and S. Subramanya. "Mushroom diversity in the Biligiri rangana hills of Karnataka (India)." Journal of Applied and Natural Science 9, no. 3 (September 1, 2017): 1381–87. http://dx.doi.org/10.31018/jans.v9i3.1371.
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Evergreen forests of Biligiri rangana hills (BR hills) spread over an area of 540 sq. KM over eastern most edge of Western Ghats in Karnataka. Climatic conditions are more favorable for establishment of mushrooms and complete their life cycle. In this study, fourteen mushroom species were collected from BR hills region during monsoon (June through September 2013) with the help of Solega tribe inhabited the region since many years. Of the fourteen mushrooms, two mushrooms were identified as Ganoderma lucidum and Polyporous flabelliformis based on their phenotypic characters. The other 12 mushrooms were identified by ITS (Internal Transcribed spacer)region sequence homology as Termitomyces sp. (BRM-3)., Auricularia delicate (BRM-4), Termitomyces microcarpus (BRM-5), Amanita sp. (BRM-6), Podoscypha petalodes (BRM-7), Agaricaceae sp. (BRM-8), Macrolepiota sp.(BRM-9), Calvatia holothurioides (BRM-10), Gymnopillus crociphyllus (BRM-11), Coprinus comatus (BRM-12), Gyrodontium sacchari (BRM-13) and Clitocybeafffellea (BRM-14). Among the fourteen mushrooms, three species viz., Termito-myces species, Auricularia delicate and Termitomyces microcarpus were edible. The others were non edible/poisonous species. This study reports the diverse mushroom species as addition to biodiversity at BR hills.
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Wong, Kit Man, Geoffrey Liu, Jonghun John Lee, Osvaldo Espin-Garcia, Yonathan Brhane, Dangxiao Cheng, Zhuo Chen, et al. "BRM promoter insertion/deletion polymorphisms in hepatocellular carcinoma risk and survival." Journal of Clinical Oncology 32, no. 3_suppl (January 20, 2014): 225. http://dx.doi.org/10.1200/jco.2014.32.3_suppl.225.
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225 Background: MEF2D and HDAC9 regulate the expression of BRM, the catalytic subunit of SWI/SNF (chromatin remodeling complex). MEF2D binding sites are created in the BRM promoter by two germline insertion/deletion polymorphisms (BRM-741, BRM-1321), which mediate epigenetic silencing. We recently identified BRM as a potential drug target and a susceptibility gene for lung and head and neck cancers, while others reported its association with HCC risk in Asians. BRM also correlates with prognosis in lung and esophageal cancers (ASCO 2013; abstracts 11057, 4077). In this analysis, we assessed the effects of the BRM promoter variants on risk and overall survival (OS) in HCC from a North American centre (Toronto). Methods: We conducted a case-control study with 266 histologically confirmed HCC cases and 536 age/sex distribution-matched healthy controls. Survival of the cases was obtained from medical records. Association between the BRM polymorphisms and HCC risk was analyzed by multivariate logistic regression adjusted for age, sex, race, smoking and BMI; their impact on OS was evaluated by Cox proportional hazard regression adjusted for age, sex, treatment intent and Hepatitis B status. Results: Median age was 62 years; 83% were male. Hepatitis B and C infections affected 34% and 31% of cases, respectively. 83% of patients were Child Pugh A at diagnosis, and 66% received initial curative therapy (surgical resection rate 32%). There were 13% deaths at a median follow-up of 24.1 months. There was no significant association between BRM polymorphisms and HCC risk: the adjusted risk odds ratios of the homozygous BRM variants, relative to wild-type, were 0.87 (95% CI: 0.53-1.45; BRM-741) and 1.01 (95% CI: 0.78-1.29; BRM-1321), and 0.94 (95% CI: 0.48-1.86) for the double homozygotes vs. double wild-type. The adjusted hazard ratios for OS were 5.77 (95% CI: 2.9-11.5; BRM-741) and 4.09 (95% CI: 2.2-7.5; BRM-1321) for each variant allele; the double homozygotes were also highly associated with OS compared to double wild-type (p<0.0001). Conclusions: Two functional BRM promoter polymorphisms did not increase the risk of HCC. However, they were strongly associated with OS despite short median follow-up. SPC and RH are co-senior authors.
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Segedi, Maja, Laura N. Anderson, Osvaldo Espin-Garcia, Ayelet Borgida, Teresa Bianco, Dangxiao Cheng, Zhuo Chen, et al. "Functional BRM promoter polymorphisms, pancreatic adenocarcinoma risk, and survival." Journal of Clinical Oncology 32, no. 3_suppl (January 20, 2014): 222. http://dx.doi.org/10.1200/jco.2014.32.3_suppl.222.
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222 Background: Variant alleles of two promoter polymorphisms in the BRM gene (BRM-741, BRM -1321), create MEF2D transcription binding sites that lead to epigenetic silencing of BRM, the key catalytic component of the SWI/SNF chromatin remodeling complex (PMID:23524580). BRM suppression can be reversed pharmacologically (PMID: 21478905). Our group and others have reported associations with lung, head and neck, and hepatocellular cancer risk (PMIDs: 21478907, 23322154, 23359823). We have also reported associations with lung and esophageal cancer prognosis (ASCO 2013; abstr 11057 and 4077). In this analysis, we assessed risk and survival associations with pancreatic cancer. Methods: A population-based case-control study was conducted in Ontario with 623 histologically-confirmed pancreatic adenocarcinoma cases and 1192 age/gender distribution-matched controls (PMID: 23908141). Survival of cases was obtained through the Ontario Cancer Registry. Logistic and Cox proportional hazard regression models were fitted, adjusting for relevant covariates. Results: Median age was 65 years; 52% were male; 53% had received a curative resection; Stage I (8%), II (55%), III (14%), IV (23%); 79% received chemotherapy; 83% had died. In the risk analysis, the adjusted odds ratios were 1.01 (95%CI:0.1-2.0) and 0.96 (95%CI:0.7-1.3) for the homozygous variants of BRM-741 and BRM-1321, respectively, when each was compared to wildtype; adjusted odds ratio of double-homozygotes was 1.11 (95%CI:0.80-1.53) when compared to the double-wildtype. In contrast for the survival analysis, the hazard ratios (adjusted for age, stage, receipt of curative surgery, receipt of chemotherapy, and packyears) were 2.19 (95%CI: 1.9-2.5) for BRM-741 and 1.94 (95%CI: 1.7-2.2) for BRM-1321, per each unit increase in variant alleles. Compared with the double-wildtype, the adjusted hazard ratio for carrying no, one, and two homozygous (double-homozygous) variants were 2.14 (95%CI:1.6-2.8), 4.17 (95%CI:3.0-5.7), and 8.03 (95%CI: 5.7-11.4), respectively. Conclusions: Two functional promoter BRM polymorphisms were not associated with pancreatic adenocarcinoma risk, but are strongly associated with survival.
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Tabuloc, Christine A., Yao D. Cai, Rosanna S. Kwok, Elizabeth C. Chan, Sergio Hidalgo, and Joanna C. Chiu. "CLOCK and TIMELESS regulate rhythmic occupancy of the BRAHMA chromatin-remodeling protein at clock gene promoters." PLOS Genetics 19, no. 2 (February 21, 2023): e1010649. http://dx.doi.org/10.1371/journal.pgen.1010649.
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Circadian clock and chromatin-remodeling complexes are tightly intertwined systems that regulate rhythmic gene expression. The circadian clock promotes rhythmic expression, timely recruitment, and/or activation of chromatin remodelers, while chromatin remodelers regulate accessibility of clock transcription factors to the DNA to influence expression of clock genes. We previously reported that the BRAHMA (BRM) chromatin-remodeling complex promotes the repression of circadian gene expression in Drosophila. In this study, we investigated the mechanisms by which the circadian clock feeds back to modulate daily BRM activity. Using chromatin immunoprecipitation, we observed rhythmic BRM binding to clock gene promoters despite constitutive BRM protein expression, suggesting that factors other than protein abundance are responsible for rhythmic BRM occupancy at clock-controlled loci. Since we previously reported that BRM interacts with two key clock proteins, CLOCK (CLK) and TIMELESS (TIM), we examined their effect on BRM occupancy to the period (per) promoter. We observed reduced BRM binding to the DNA in clk null flies, suggesting that CLK is involved in enhancing BRM occupancy to initiate transcriptional repression at the conclusion of the activation phase. Additionally, we observed reduced BRM binding to the per promoter in flies overexpressing TIM, suggesting that TIM promotes BRM removal from DNA. These conclusions are further supported by elevated BRM binding to the per promoter in flies subjected to constant light and experiments in Drosophila tissue culture in which the levels of CLK and TIM are manipulated. In summary, this study provides new insights into the reciprocal regulation between the circadian clock and the BRM chromatin-remodeling complex.
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Tse, Brandon C., Vivian Tam, Tiffany Tse, Lin Lu, Michael Borean, Emily Tam, Catherine Labbé, et al. "The impact of neurocognitive function on health utility scores (HUS) in Stage 4 (S4) lung cancer patients (pts) with and without brain metastases (BrM)." Journal of Clinical Oncology 35, no. 5_suppl (February 10, 2017): 225. http://dx.doi.org/10.1200/jco.2017.35.5_suppl.225.
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225 Background: As targeted therapies for S4LC pts have improved survival, the impact of health-related quality of life (HRQoL) in these pts grows in importance. In pts with BrM, loss of NCF may affect HRQoL significantly. We evaluated the relationship between NCF and HUS as a measure of HRQoL in S4LC pts. Methods: Self-reported HUS data from EQ5D-3L were obtained cross-sectionally from S4LC pts with (BrM) or without BrM (non-BrM). NCF was measured using the Hopkins Verbal Learning Test – Revised (HVLT-R), the Controlled Oral Word Association Test (COWAT) and Trail Making Tests (TMT-A/B). NCF scores were correlated with HUS (Pearson Coefficient, R). Results: BrM (n = 54) and non-BrM (n = 40) patients had similar demographics- overall median age was 61 (range 33-89) years; 59% were female; 45% had EGFR/ALK alterations; BrM pts were treated with whole brain (n = 20), stereotactic radiation (n = 19), both (n = 6), or sole use of systemic agents (n = 6); 3 were observed; 7 had BrM resection. Overall HUS were similar between BrM and non-BrM groups (mean HUS (mHUS): 0.77 vs. 0.78; p = 0.86). However, pts with stable brain disease had higher HUS than those with progressive brain disease (mHUS: 0.80 (n = 36) vs 0.69 (n = 17); p = 0.045). There was a trend towards lower HUS in symptomatic vs. asymptomatic BrM (mHUS: 0.70 (n = 10) vs. 0.78 (n = 43); p = 0.07). Multiple correlations between NCF scores and HUS were found. HLVT-Total Recall correlated with HUS in BrM but not non-BrM (R=0.35, p = 0.01; vs. non- R=0.04, p = 0.84 respectively) as did the HLVT-Recognition (BrM: R=0.32, p = 0.03 vs. non-BrM: R=0.13, p = 0.51). In contrast, TMT-A/B were associated with HUS in both BrM (p = 0.03, 0.06) and non-BrM pts (p = 0.001, 0.03). COWAT was associated with HUS only when all pts were analyzed together (p = 0.04). Conclusions: In S4LC pts, HUS were correlated with multiple measures of NCF. The impact of uncontrolled brain disease and poor NCF on HUS demonstrates that this measure has clinical utility, with important HRQoL implications as metastatic lung cancer pts live longer.
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Wong, Kit Man, Xiaoping Qiu, Dangxiao Cheng, Abul Kalam Azad, Prakruthi R. Palepu, Maryam Mirshams, Devalben Patel, et al. "The effect of two BRM promoter variants on the risk of stage I/II upper aerodigestive tract cancers." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 10522. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.10522.
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10522 Background: BRM is a key subunit of the chromatin remodeling complex SWI/SNF and a putative tumor suppressor gene that is silenced in 15-20% of many solid tumors (PMID 15722796). Evidence suggests that it is epigenetically regulated, as two BRM promoter insertion variants (BRM-741 and BRM-1321) may lead to gene silencing by recruiting histone deacetylases. The presence of both homozygous BRM-741 and BRM-1321 highly correlate with loss of BRM expression and function in lung tumors, while increasing smoking-related lung cancer by two-fold (PMID 21478907). Also, the pharmacologic reversal of epigenetic changes of BRM offers a potential novel therapeutic approach (PMID 21478905). We assessed whether these BRM variants are associated with the risk of upper aerodigestive tract cancers, focusing on Stage I/II tumors that would most benefit from new screening and prevention strategies. Methods: BRM was genotyped by qPCR using TaqMan probes. 1,008 controls were matched to 595 cases by frequency distribution based on age, gender and smoking status. Multivariate logistic regression generated adjusted odds ratios (aOR). Results: The 595 cases were: 115 esophageal, 278 lung, and 202 head and neck cancers. 51% were adenocarcinomas; 60% were Stage I. The frequency of homozygozity was: BRM-741, 26%; BRM-1321, 23%; both variants, 15%. In the combined analysis, there was significant correlation between malignancy and homozygous BRM-741 (aOR 1.91 (95%CI 1.3-2.4); p=0.001) or BRM-1321 (aOR 1.94 (95%CI 1.4-2.7; p=3x10E-4). Being homozygous for both BRM variants carried an even greater risk (aOR 2.45 (95%CI 1.6-3.9); p=1x10E-5). This correlation was similar for adenocarcinomas (aOR 2.53 (95%CI 1.4-4.2); p=6x10E-4) and squamous cell carcinomas (aOR 2.33 (95%CI 1.3-4.4); p=8x10E-4). The increased cancer risk was also similar between these subgroups: head and neck, esophageal and lung cancers; Stage I and II patients; smokers and non-smokers. Conclusions: The two homozygous BRM variants increase the risk of early stage upper aerodigestive tumors by more than two-fold independent of smoking status. BRM promoter variants and their potential epigenetic effect may be early events in the evolution of these cancers.
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Cuffe, Sinead, Lu Cheng, Abul Kalam Azad, Yonathan Brhane, Dangxiao Cheng, Zhuo Chen, Xin Qiu, et al. "Effect of BRM promoter variants on survival outcomes of stage III-IV non-small cell lung cancer (NSCLC) patients." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 11057. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.11057.
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11057 Background: BRM, a key catalytic subunit of the SWI/SNF chromatin remodeling complex, is a putative tumor susceptibility gene in NSCLC. Loss of BRM expression occurs in 15% of NSCLC, and has been linked to adverse outcome. Recently, our group has shown that variants of two novel BRM promoter insertion polymorphisms (BRM-741, BRM-1321) lead to loss of BRM expression by recruiting histone deacetylases; individuals carrying homozygous variants for both polymorphisms have doubled NSCLC risk; pharmacological reversal of these epigenetic changes is a potentially viable therapeutic strategy. We thus evaluated the effect of BRM promoter variants on survival outcomes of advanced NSCLC patients, where initial clinical trials are likely to be focused. Methods: 564 stage III-IV NSCLC patients were genotyped for the BRM promoter variants using Taqman. Association of BRM variants and overall (OS) and progression-free survival (PFS) were assessed using Cox proportional hazard models adjusted for prognostic variables. Results: Among our patients, 73% were Caucasian, 52% male, median age 63yrs, 55% stage IV disease, and 67% adenocarcinoma. Median OS was 1.6yrs; median follow up, 3.6yrs. The frequency of homozygosity was BRM-741, 23%; BRM-1321, 21%; both, 12%. Homozygous variants of BRM-741 were strongly associated with worse OS (adjusted HR [aHR] 2.3 [p=2x10E-8]) and PFS (aHR 2.0 [p=2x10E-7]) compared to the wild types. Similar findings were observed for BRM-1321 homozygous variants (aHR for OS 1.8 [p=8x10E-5] and aHR for PFS 1.6 [p=2x10E-4]). Carrying homozygous variants of both BRM-741 and BRM-1321 was associated with substantially worse OS (aHR 2.3 [p=1x10E-5]) and PFS (aHR 2.2 [p=3x10E-6]), with similar associations seen among the stage III (aHR for OS 2.3 [p=6x10E-6]) and stage IV (aHR for OS 2.5 [p=5x10E-6]) patients. Conclusions: The same two homozygous BRM promoter variants that are associated with increased risk of NSCLC are also strongly associated with adverse OS and PFS in this cohort of stage III-IV NSCLC patients. Validation of results in a clinical trial dataset is underway, and will better elucidate the prognostic significance of these BRM promoter variants.
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FERNANDES, JOÃO PEDRO TAVARES, ADRIANO STEPHAN NASCENTE, MARTA CRISTINA CORSI DE FILIPPI, ANNA CRISTINA LANNA, VINÍCIUS SILVA SOUSA, and MARIANA AGUIAR SILVA. "PHYSIO-AGRONOMIC CHARACTERIZATION OF UPLAND RICE INOCULATED WITH MIX OF MULTIFUNCTIONAL MICROORGANISMS." Revista Caatinga 33, no. 3 (September 2020): 679–89. http://dx.doi.org/10.1590/1983-21252020v33n311rc.
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ABSTRACT Multifunctional microorganisms can contribute significantly to improve plant performance and are innovative technology for sustainable development. Thus, objective of this study was to determine the effect of bioagents applied alone or in mix on the performance of upland rice. The experiment was conducted in a greenhouse in a completely randomized design with four replications. The 26 treatments consisted of the rhizobacteria Bacillus sp. (BRM 32109, BRM 32110 and 1301), Azospirillum sp. (1381), Azospirillum brasilense (Ab-V5), Pseudomonas sp. (BRM 32112), Pseudomonas fluorescens (BRM 32111), Burkholderia pyrrocinia (BRM 32113), Serratia sp. (BRM 32114), and a fungal genus formed by a pool of Trichoderma asperellum (T-06, T-09, T-12, and T-52), applied alone or in mix, plus a control treatment without microorganism application. The most effective treatments were the mixes of microorganisms 1301 + Ab-V5 and BRM 32114 + pool of Trichoderma asperellum, as they provided an average increase of 123 and 88% in the number of panicles and 206 and 167% in the grain yield of upland rice plants, respectively. Mixes of 1301 + Ab-V5, BRM 32114 + Trichoderma asperellum pool, BRM 32110 + BRM 32114, BRM 32110 + Ab-V5, 1301 + BRM 32110 and 1381 + Trichoderma asperellum pool also provided better morphophysiological performance in rice plants (photosynthetic rate, carboxylation efficiency, number of tillers, shoot dry biomass and nutrient content in shoot and root). Therefore, the use of multifunctional microorganisms in the management of upland rice was efficient in its ability to provide better development of plants.
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Papoulas, O., S. J. Beek, S. L. Moseley, C. M. McCallum, M. Sarte, A. Shearn, and J. W. Tamkun. "The Drosophila trithorax group proteins BRM, ASH1 and ASH2 are subunits of distinct protein complexes." Development 125, no. 20 (October 15, 1998): 3955–66. http://dx.doi.org/10.1242/dev.125.20.3955.
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The trithorax group gene brahma (brm) encodes an activator of Drosophila homeotic genes that functions as the ATPase subunit of a large protein complex. To determine if BRM physically interacts with other trithorax group proteins, we purified the BRM complex from Drosophila embryos and analyzed its subunit composition. The BRM complex contains at least seven major polypeptides. Surprisingly, the majority of the subunits of the BRM complex are not encoded by trithorax group genes. Furthermore, a screen for enhancers of a dominant-negative brm mutation identified only one trithorax group gene, moira (mor), that appears to be essential for brm function in vivo. Four of the subunits of the BRM complex are related to subunits of the yeast chromatin remodeling complexes SWI/SNF and RSC. The BRM complex is even more highly related to the human BRG1 and hBRM complexes, but lacks the subunit heterogeneity characteristic of these complexes. We present biochemical evidence for the existence of two additional complexes containing trithorax group proteins: a 2 MDa ASH1 complex and a 500 kDa ASH2 complex. These findings suggest that BRM plays a role in chromatin remodeling that is distinct from the function of most other trithorax group proteins.
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Dankner, Matthew, Sarah Maritan, Rebecca Zhuang, Maxime Caron, Neibla Priego, Manuel Valiente, Kevin Petrecca, and Peter Siegel. "BSCI-10. Invasive growth of brain metastases is driven by cancer cell-pSTAT3+ reactive astrocyte crosstalk." Neuro-Oncology Advances 3, Supplement_3 (August 1, 2021): iii3. http://dx.doi.org/10.1093/noajnl/vdab071.009.
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Abstract Background Brain metastases (BrM) with a highly invasive (HI) histological growth pattern are associated with poor prognosis compared to minimally invasive (MI) masses. Compared to MI lesions, HI BrM form greater contacts with cells in the peritumoral brain, particularly reactive astrocytes (RAs). RAs expressing phosphorylated STAT3 (pSTAT3+RAs) have been shown to promote BrM colonization. Here, we investigate the role of pSTAT3+RAs in promoting invasive growth of HI BrM. Methods We performed immunohistochemistry to identify pSTAT3+RAs in HI and MI human and patient-derived xenograft BrM. We assessed how pharmacological STAT3 inhibition or RA-specific STAT3 genetic ablation affected HI and MI BrM growth in vivo. scRNA-seq data generated from HI BrM astrocytes were integrated with published RA secretome data to identify STAT3 targets expressed by RAs that may drive invasion. Cancer cell invasion was modeled in vitro using a brain slice-tumor co-culture assay. Results HI BrM display increased pSTAT3-positivity within RAs when compared to MI lesions. Pharmacological STAT3 inhibition with Legasil (Silibinin) or genetic ablation decreased in vivo growth of HI, but not MI, BrM. Brain slice cultures treated with STAT3-activating cytokines induced cancer cell invasion, a response that was ablated following STAT3 inhibition. Chi3L1 was identified as a STAT3 target expressed by RAs. Cancer cells treated with recombinant Chi3L1 showed greater invasion into brain slice cultures compared to untreated cells. Conclusions pSTAT3+RAs are over-represented in HI BrM, rendering HI BrM preferentially sensitive to STAT3 inhibition. pSTAT3+RAs functionally contribute to BrM invasion within the brain, in part through Chi3L1-mediated activity. This work identifies STAT3 and Chi3L1 as clinically relevant therapeutic targets in management of HI BrM.
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Oktavia, Nova. "Gambaran Faktor – Faktor Keterlambatan Waktu Penyediaan Berkas Rekam Medis Poliklinik Jantung Di Rumah Sakit Rafflesia Kota Bengkulu Tahun 2017." Jurnal Manajemen Informasi Kesehatan (Health Information Management) 2, no. 1 (June 22, 2017): 8–15. http://dx.doi.org/10.51851/jmis.v2i1.29.
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Berdasarkan observasi secara langsung di unit rekam medis (RM) Rumah Sakit Rafflesia Bengkulu pada proses penyediaan berkas rekam medis (BRM) untuk pasien rawat jalan poliklinik jantung dari 10 BRM yang diamati terdapat 8 BRM yang melebihi standar waktu penyediaan yaitu 10 menit. Tujuan penelitian ini adalah untuk mengetahui gambaran faktor – faktor keterlambatan waktu penyediaan BRM poliklinik jantung diRumah Sakit Rafflesia Kota Bengkulu Tahun 2017. Jenis penelitian yang digunakan adalah Observasional Deskriptif dengan rancangan Cross-Sectional, Populasi dalam penelitian yaitu 10 petugas RM yang melayani pasien rawat jalan dan BRM yang disediakan oleh petugas rawat jalan, sampel sebanyak 105 BRM poliklinik jantung dengan teknik pengambilan Non Probality sampling dengan jenis Consecutive sampling. Menggunakan data primer, diolah secara univariat. Penelitian dilaksankan bulan Juli Tahun 2017 di Rumah Sakit Rafflesia Kota Bengkulu, bertempat dipendaftaran pasien rawat jalan. Hasil analisa univariat, dari 10 petugas RM rawat jalan hanya satu berpendidikan D III Rekam Medis dan mayoritas masa kerja petugasnya ≤ 5 tahun, pada saat pengambilan BRM di ruangan filing, dari 105 BRM mayoritas berkas sulit ditemui pada rak penyimpanan yaitu 62 (59,1 %) BRM dan 105 BRM 62 (59,1%) berkas lambat disediakan oleh petugas rawat jalan. Diharapkan penambahan SDM lulusan D III RM dan petugas Non RM diikuti pelatihan atau seminar, Sebaiknya ada tanda petunjuk untuk berkas keluar (outguide/tracer).
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Van Swearingen, Amanda, Eric Routh, Maria Sambade, Steven Vensko, Marni McClure, Mark Woodcock, Shengjie Chai, et al. "BSCI-06 COMPREHENSIVE ANALYSIS OF THE IMMUNOGENOMICS OF TRIPLE NEGATIVE BREAST CANCER BRAIN METASTASES FROM LCCC1419." Neuro-Oncology Advances 4, Supplement_1 (August 1, 2022): i2. http://dx.doi.org/10.1093/noajnl/vdac078.006.
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Abstract BACKGROUND Triple negative breast cancer (TNBC) lacks expression of hormone receptors (estrogen and progesterone receptors, ER and PR) and HER2. Almost 50% of patients with metastatic TNBC will develop brain metastases (BrM), often with concurrent progressive extracranial disease. While immunotherapy has shown promise in the treatment of advanced TNBC, the immune profile of BrM remains largely unknown. To inform the development of immunotherapy strategies in this aggressive disease, we characterized the genomic and immune landscape of TNBC BrM and matched primary tumors. METHODS Formalin-fixed, paraffin-embedded samples of BrM and primary tumors of patients with clinical TNBC (n=25, n=9 matched pairs) from the LCCC1419 biobank at UNC-Chapel Hill were analyzed by whole exome (WES) and RNA sequencing, with matched blood DNA sequenced for identification of somatic variants. Mutational and copy number alteration analyses, neoantigen prediction, and transcriptomic analysis of the tumor immune microenvironment were performed. RESULTS Primary and BrM tissues were confirmed as TNBC and of the basal intrinsic subtype. Compared to primary tumors, BrM demonstrated higher tumor mutational burden. Neoantigen prediction showed elevated cancer testis antigen- and endogenous retrovirus-derived MHC class I-binding peptides in both primary tumors and BrM, and predicted single nucleotide variants (SNV)-derived peptides were significantly higher in BrM. BrM demonstrated reduced immune gene signature expression, although a signature associated with fibroblast-associated wound healing was elevated in BrM. Metrics of T and B cell receptor diversity were also reduced in BrM. CONCLUSIONS BrM harbored higher mutational burden and SNV-derived neoantigen expression along with reduced immune gene signature expression relative to primary TNBC. Further research will expand these findings to other breast cancer subtypes. Exploration of immunomodulatory approaches including vaccine applications and immune checkpoint inhibition to enhance anti-tumor immunity in TNBC BrM are warranted.
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Halliday, Gary M., Yue Zhou, Paul W. Sou, Xiao X. J. Huang, Sabita Rana, Matthew J. Bugeja, Nicole Painter, et al. "The absence of Brm exacerbates photocarcinogenesis." Experimental Dermatology 21, no. 8 (July 10, 2012): 599–604. http://dx.doi.org/10.1111/j.1600-0625.2012.01522.x.
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CYONG, Jong-Chl. "New BRM from Kampo-herbal medicine." Folia Pharmacologica Japonica 110, supplement (1997): 87–92. http://dx.doi.org/10.1254/fpj.110.supplement_87.
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Ozaki, Shoichi, Takahiro Okazaki, and Kazuwa Nakao. "Biological response modifiers (BRM) as antigens." Cancer Immunology Immunotherapy 40, no. 4 (July 1995): 219–27. http://dx.doi.org/10.1007/bf01519895.
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Ozaki, S., Takahiro Okazaki, and Kazuwa Nakao. "Biological response modifiers (BRM) as antigens." Cancer Immunology, Immunotherapy 40, no. 4 (April 1, 1995): 219–27. http://dx.doi.org/10.1007/s002620050166.
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Rudolf, Martin, and Christine A. Curcio. "Esterified Cholesterol Is Highly Localized to Bruch's Membrane, as Revealed by Lipid Histochemistry in Wholemounts of Human Choroid." Journal of Histochemistry & Cytochemistry 57, no. 8 (April 13, 2009): 731–39. http://dx.doi.org/10.1369/jhc.2009.953448.
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Accumulation of neutral lipids in Bruch's membrane (BrM) is a major age change in human retina and contributes to the formation of extracellular lesions associated with age-related macular degeneration. We developed a BrM–choroid wholemounting technique suitable for reliable staining and evaluated different fluorescent lipid dyes for topographic semiquantitative analysis of BrM lipids. Thin BrM–choroid complexes with partially stripped choroid from 10 aged donor eyes were prepared with an optimized wholemounting technique. Preparation quality was monitored by examining 1-μm-thick sections of representative samples. The staining patterns of Nile Red, BODIPY 493/503, filipin for unesterified cholesterol (UC-F), filipin for esterified cholesterol (EC-F), and Oil Red O in wholemounts were compared with their staining patterns in chorioretinal sections, using wide-field epi-fluorescence microscopy. Wholemounts exhibited optimal flatness on the BrM side. Reduced tissue thickness allowed reliable dye penetration and staining of BrM. Only EC-F was with high specificity localized to BrM and demonstrated an intense and distinct granular staining pattern not previously appreciated in chorioretinal sections. All other lipid dyes also stained choroidal or retinal tissue intensely. No dye provided perfect characteristics in regard to representing all neutral lipid classes present in BrM or to fluorescence intensity. Nevertheless, only EC-F was highly localized to BrM with a specific granular pattern. Because direct assays indicate that esterified cholesterol is abundantly present in BrM, we consider EC-F the most valuable choice for analyzing neutral lipid deposits in human BrM.
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Dankner, Matthew, Maxime Caron, Tariq Al-Saadi, WenQing Yu, Veronique Ouellet, Phuong Uyen Le, Rima Ezzeddine, et al. "65. INVASIVE HISTOPATHOLOGY DRIVES POOR OUTCOMES IN SURGICALLY RESECTED BRAIN METASTASES." Neuro-Oncology Advances 2, Supplement_2 (August 2020): ii13—ii14. http://dx.doi.org/10.1093/noajnl/vdaa073.052.
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Abstract BACKGROUND Brain metastasis (BrM) patients treated with surgery and radiotherapy frequently experience local recurrence (LR), leptomeningeal metastasis (LM), and poor overall survival (OS). We sought to correlate the presence of invasive or circumscribed histopathological growth pattern, observed in the BrM lesion and surrounding brain, with these outcomes, and to study molecular mediators of parenchymal invasion. METHODS We assessed the HGP of H&E-stained slides from 164 surgically resected BrM from 147 patients. HGP was correlated with incidence of LR, LM and OS. Single-cell RNA sequencing (scRNAseq) was performed on three invasive HGP patients, sampling the metastasis center (MC) and surrounding brain (SB) outside of the contrast-enhancing region. Orthotopic patient-derived xenograft models (OPDX) were established from N=30 brain metastasis via intracranial propagation. RESULTS 56/164 BrM specimens (34%) showed a circumscribed growth pattern between the tumor and adjacent brain (cHGP) while 108/164 (66%) showed significant invasion of tumor lobules or single cells into the brain parenchyma (iHGP). iHGP was associated with LR, LM and shortened OS in BrM patients. OPDX models of BrM retain features of patient BrM, including HGP. scRNAseq identified abundant cancer cells in SB that overexpressed a number of genes involved in cell survival, invasion and metastasis compared to matched cancer cells in MC. Validation of these targets with immunohistochemistry in patient and OPDX tissues revealed cold-inducible RNA binding protein (CIRBP) overexpression in iHGP patient and OPDX BrM. Modulation of CIRBP expression in OPDX and cell line models of iHGP BrM delayed BrM progression and extended OS. CONCLUSION iHGP is a poor prognostic indicator in patients with surgically resected BrM, establishing HGP as an important prognostic factor that should be considered by clinicians treating BrM patients. We identify CIRBP as a functional mediator of this process.
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Puspitasari, Nurmalinda. "Evaluasi Tingkat Ketidaktepatan Pemberian Kode Diagnosis Dan Faktor Penyebab Di Rumah Sakit X Jawa Timur." Jurnal Manajemen Kesehatan Yayasan RS.Dr. Soetomo 3, no. 2 (October 23, 2017): 158. http://dx.doi.org/10.29241/jmk.v3i1.77.
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ABSTRAKKetepatan kode diagnosa dapat berpengaruh terhadap analisis pembiayaan pelayanan kesehatan khusus dalam kelancaran proses pengklaiman, pelaporan nasional morbiditas dan mortalitas, tabulasi data pelayanan kesehatan bagi proses evaluasi perencanaan pelayanan medis, menentukan bentuk pelayanan yang harus direncanakan dan dikembangkan sesuai kebutuhan zaman dan untuk penelitian epidemiologi dan klinis.. Tujuan penelitian ini adalah mengevaluasi tingkat ketidaktepatan dan faktor-faktor penyebab ketidaktepatan pemberiankode diagnosis di Rumah Sakit X jawa Timur. Jenis penelitian adalah penelitian deskriptif dengan studi retrospektif. Populasi adalah seluruh BRM bulan Januari-Maret 2017 dan sampel yang diambil sebanyak 634 BRM rawat jalan dan rawat inap. Analisis data secara deskriptif. Hasil penelitian menunjukkanterdapat 504 kode diagnosis terkode pada BRM dan 130 tidak terkode pada BRM. Tingkat ketidaktepatan kode diagnosis didapat sebanyak 305 BRM (61%) yang tepat, 31 BRM (6%) yang tepat sebagian, dan 168 BRM (33%) yang tidak tepat. Faktor-faktor penyebab meliputi pengetahuancoder, ketidaklengkapan informasipenunjang medis, ketidaksesuain penggunaan singkatan dengan daftar singkatan Rumah Sakit, dan keterbacaan diagnosis.
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Elfring, L. K., R. Deuring, C. M. McCallum, C. L. Peterson, and J. W. Tamkun. "Identification and characterization of Drosophila relatives of the yeast transcriptional activator SNF2/SWI2." Molecular and Cellular Biology 14, no. 4 (April 1994): 2225–34. http://dx.doi.org/10.1128/mcb.14.4.2225-2234.1994.
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The Drosophila brahma (brm) gene encodes an activator of homeotic genes that is highly related to the yeast transcriptional activator SWI2 (SNF2), a potential helicase. To determine whether brm is a functional homolog of SWI2 or merely a member of a family of SWI2-related genes, we searched for additional Drosophila genes related to SWI2 and examined their function in yeast cells. In addition to brm, we identified one other Drosophila relative of SWI2: the closely related ISWI gene. The 1,027-residue ISWI protein contains the DNA-dependent ATPase domain characteristic of the SWI2 protein family but lacks the three other domains common to brm and SWI2. In contrast, the ISWI protein is highly related (70% identical) to the human hSNF2L protein over its entire length, suggesting that they may be functional homologs. The DNA-dependent ATPase domains of brm and SWI2, but not ISWI, are functionally interchangeable; a chimeric SWI2-brm protein partially rescued the slow growth of swi2- cells and supported transcriptional activation mediated by the glucocorticoid receptor in vivo in yeast cells. These findings indicate that brm is the closest Drosophila relative of SWI2 and suggest that brm and SWI2 play similar roles in transcriptional activation.
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Elfring, L. K., R. Deuring, C. M. McCallum, C. L. Peterson, and J. W. Tamkun. "Identification and characterization of Drosophila relatives of the yeast transcriptional activator SNF2/SWI2." Molecular and Cellular Biology 14, no. 4 (April 1994): 2225–34. http://dx.doi.org/10.1128/mcb.14.4.2225.
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The Drosophila brahma (brm) gene encodes an activator of homeotic genes that is highly related to the yeast transcriptional activator SWI2 (SNF2), a potential helicase. To determine whether brm is a functional homolog of SWI2 or merely a member of a family of SWI2-related genes, we searched for additional Drosophila genes related to SWI2 and examined their function in yeast cells. In addition to brm, we identified one other Drosophila relative of SWI2: the closely related ISWI gene. The 1,027-residue ISWI protein contains the DNA-dependent ATPase domain characteristic of the SWI2 protein family but lacks the three other domains common to brm and SWI2. In contrast, the ISWI protein is highly related (70% identical) to the human hSNF2L protein over its entire length, suggesting that they may be functional homologs. The DNA-dependent ATPase domains of brm and SWI2, but not ISWI, are functionally interchangeable; a chimeric SWI2-brm protein partially rescued the slow growth of swi2- cells and supported transcriptional activation mediated by the glucocorticoid receptor in vivo in yeast cells. These findings indicate that brm is the closest Drosophila relative of SWI2 and suggest that brm and SWI2 play similar roles in transcriptional activation.
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Dankner, Matthew, Paul Savage, April Rose, Mathieu Lajoie, Roberto Diaz, Morag Park, Ian Watson, Marie-Christine Guiot, Kevin Petrecca, and Peter Siegel. "TMOD-41. ORTHOTOPIC PATIENT-DERIVED XENOGRAFT MODELS OF BRAIN METASTASIS: PLATFORMS FOR PRECISION ONCOLOGY AND UNDERSTANDING TUMOR BIOLOGY." Neuro-Oncology 21, Supplement_6 (November 2019): vi272. http://dx.doi.org/10.1093/neuonc/noz175.1140.
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Abstract RATIONALE Brain metastasis (BrM) occurs in 10–20% of cancer patients and results in median survival times of less than 1 year. In order to accurately develop novel treatment strategies, there is an urgent need to establish animal models of BrM that resemble the human disease. OBJECTIVES: We sought to establish orthotopic patient-derived xenografts (PDX) models of BrM from diverse solid cancers to understand biological characteristics of BrM and to test novel drug candidates in their ability to treat BrM. METHODS 35 PDXs were established by subcutaneous or mammary fat pad implantation and by intracranial injection. PDXs were validated by immunohistochemistry of routine pathological markers in patient specimens and matched primary and intracranial PDXs. PDXs were applied for precision medicine in class II BRAF mutant tumours treated with targeted therapy and in the pre-clinical development of a novel therapeutic agent, DZ-2384, which may have applications in treating BrM. They were also used to understand the underlying biology of leptomeningeal dissemination from parenchymal BrM. RESULTS PDXs reveal strong similarity to patient specimens by IHC staining. Class II BRAF mutant PDXs are optimally sensitive to BRAF and MEK inhibitors compared to either agent alone. DZ-2384 is effective in slowing the progression of breast cancer BrM. PDXs that most efficiently invade the leptomeninges display loss of E-Cadherin expression, suggesting the role of an epithelial-mesenchymal transition in this process. CONCLUSIONS PDXs of BrM represent important models that can be employed to test novel therapeutics and to improve understanding of molecular mechanisms engaged by BrM.
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Dankner, Matthew, Maxime Caron, Tariq Al-Saadi, WenQing Yu, Veronique Ouellet, Rima Ezzeddine, Matthew G. Annis, et al. "BIOM-03. INVASIVE HISTOPATHOLOGY DRIVES POOR OUTCOMES IN SURGICALLY RESECTED BRAIN METASTASES." Neuro-Oncology 22, Supplement_2 (November 2020): ii1—ii2. http://dx.doi.org/10.1093/neuonc/noaa215.003.
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Abstract BACKGROUND Surgery as a single modality for the treatment of brain metastases (BrM) results in local recurrence (LR) in 60% of patients. These failure rates are reduced by half with post-operative radiotherapy. The non-invasive nature of BrM has led to the assumption that local recurrence is caused by spillage of cancer cells into the surgical cavity at the time of surgery. We present evidence suggesting that invasion of metastatic cancer cells into the adjacent brain is present in the majority of BrM and is associated with LR, leptomeningeal metastasis (LM), and overall survival (OS). METHODS We assessed the histopathological growth pattern (HGP) of 164 surgically resected BrM. HGP was correlated with LR, LM and OS. Single-cell transcriptomics (scRNAseq) was performed on 15,615 cells from metastasis center (MC) and surrounding brain (SB) adjacent to the tumor. N=30 orthotopic patient-derived xenograft models (OPDX) were established from BrM. RESULTS 56/164 (34%) BrM specimens showed a minimally invasive (MI) HGP between the tumor and adjacent brain while 108/164 (66%) showed significant invasion of tumor lobules or single-cells into the brain (HI-HGP). HI-HGP was associated with LR, LM and shortened OS in BrM patients. scRNAseq identified abundant cancer cells in SB that overexpressed pathways and genes involved in cell survival and stress adaptation compared to matched cancer cells in MC. Validation of these targets with immunohistochemistry in patient and OPDX tissues revealed cold-inducible RNA binding protein (CIRBP) overexpression in HI-HGP patient and OPDX BrM. Modulation of CIRBP expression in OPDX and cell line models of HI-HGP BrM delayed BrM progression and extended OS. CONCLUSION HI-HGP is a poor prognostic indicator in patients with surgically resected BrM, establishing HGP as an important prognostic factor that should be considered by clinicians treating BrM patients. We identify CIRBP as a functional mediator of this process.
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Chehade, Rania, Maleeha A. Qazi, Marguerite Ennis, Sharon Nofech-Mozes, and Katarzyna Jerzak. "Abstract P5-13-17: PD-L1 expression in breast to brain metastases." Cancer Research 82, no. 4_Supplement (February 15, 2022): P5–13–17—P5–13–17. http://dx.doi.org/10.1158/1538-7445.sabcs21-p5-13-17.
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Abstract Background Brain metastases (BrM) are a major cause of morbidity and mortality in women with breast cancer. Immunotherapy has the potential for intracranial efficacy among patients with breast cancer since intracranial response to immunotherapy has been observed among patients with other solid tumors. The aim of the study is to analyze the immunohistochemical expression of programmed death ligand 1 (PD-L1), a predictive biomarker of response to immunotherapy, in breast cancer BrMs. Methods A retrospective cohort study of consecutive patients who underwent surgery for breast cancer BrM at Sunnybrook Health Sciences Centre between July 1999 and June 2013 were identified through the Anatomic Pathology departmental database. A tissue microarray using 1um cores was obtained. Immunohistochemical expression of PD-L1 in BrM tissue was assessed in triplicate; PD-L1 positive status was defined as PD-L1 expression ≥1% in tumor infiltrating cells as a percentage of tumor area using the Ventana SP142 antibody. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2) status was determined using 2018 ASCO/CAP guidelines. Results The median patient age at the time of BrM diagnosis was 52 (range 32-85). ER, PR and HER2 status was available in 58 of 59 cases as follows: 12 (20.3%) triple negative (TNBC), 14 (23.7%) HER2+/HR-, 14 (23.7%) HER2+/HR+, 18 (30.5%) hormone receptor (HR)+/HER2-. The majority 62.7% (n=37) of patients had a solitary BrM. The median size of BrM was 2.9 cm (range 0.3 cm to 6.2 cm) with the most common location being the cerebellum and frontal lobe. The majority of patients (n=51, 86.4%) had symptomatic BrM. The most common sites of extra-cranial metastases were bone (37%), lung (32%), liver (22%), lymph nodes (18.6%), and chest wall (3.4%). After surgical excision of BrM, 88.1% of patients received adjuvant stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT). 39% of patients received at least 1 line of systemic therapy for metastatic disease prior to the development of BrM. The median follow-up for BrM events was 16.1 months. PD-L1 status was available for all 59 patients. In the overall cohort, 9 out 59 (15.3%) breast cancer BrM were PD-L1 positive irrespective of subtype. The frequency of PD-L1 positive BrM by subtype is as follows: TNBC (n= 3/12, 25%), HER2+/HR- (n=3/14, 21.4%), HER2+/HR+ (n=1/14, 7.1%), and HR+/HER2- (n=2/18, 11.1%). Expression of PD-L1 in BrMs was not associated with patient age at the time of BrM diagnosis, size or location of the BrM, grade of the BrM nor breast cancer subtype. At 24 months, brain-specific progression-free survival (bsPFS) was 47.5% (95% CI 32.9-68.7%). When stratified by PD-L1 status, 24-month bs-PFS was 66.7% (95% CI 37.9-100%) among patients with PD-L1 positive BrM versus 42% (95% CI 26.6-67.3%) among those with PD-L1 negative BrM (log-rank p-value 0.142). Conclusion One in 7 patients in our cohort had PD-L1 positive BrM; this proportion was highest (25%) among those with TNBC. Hence, there is rationale to include patients with breast cancer BrM in clinical trials evaluating efficacy of immunotherapy. Citation Format: Rania Chehade, Maleeha A Qazi, Marguerite Ennis, Sharon Nofech-Mozes, Katarzyna Jerzak. PD-L1 expression in breast to brain metastases [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-17.
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Thouly, Caroline, Marie Le Masson, Xuelei Lai, Cristel C. Carles, and Gilles Vachon. "Unwinding BRAHMA Functions in Plants." Genes 11, no. 1 (January 13, 2020): 90. http://dx.doi.org/10.3390/genes11010090.
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The ATP-dependent Switch/Sucrose non-fermenting (SWI/SNF) chromatin remodeling complex (CRC) regulates the transcription of many genes by destabilizing interactions between DNA and histones. In plants, BRAHMA (BRM), one of the two catalytic ATPase subunits of the complex, is the closest homolog of the yeast and animal SWI2/SNF2 ATPases. We summarize here the advances describing the roles of BRM in plant development as well as its recently reported chromatin-independent role in pri-miRNA processing in vitro and in vivo. We also enlighten the roles of plant-specific partners that physically interact with BRM. Three main types of partners can be distinguished: (i) DNA-binding proteins such as transcription factors which mostly cooperate with BRM in developmental processes, (ii) enzymes such as kinases or proteasome-related proteins that use BRM as substrate and are often involved in response to abiotic stress, and (iii) an RNA-binding protein which is involved with BRM in chromatin-independent pri-miRNA processing. This overview contributes to the understanding of the central position occupied by BRM within regulatory networks controlling fundamental biological processes in plants.
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Qazi, Maleeha, Katarzyna Jerzak, and Sharon Nofech-Mozes. "61. EXPRESSION OF ANDROGEN RECEPTOR IN BREAST CANCER BRAIN METASTASIS." Neuro-Oncology Advances 2, Supplement_2 (August 2020): ii13. http://dx.doi.org/10.1093/noajnl/vdaa073.049.
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Abstract INTRODUCTION Treatment options for women with breast cancer brain metastases (BrM) are generally limited to surgery and/or radiotherapy because most systemic therapies do not cross the blood-brain barrier. Androgen receptors (ARs) are frequently expressed in breast cancer and anti-androgenic therapies have been shown to penetrate the central nervous system. In this study, we analyzed the expression of AR in breast cancer BrM to identify patients who may benefit from anti-androgenic therapies. METHODS Consecutive BrM resected in our institution (July 1999-June 2013) were identified from the Anatomic Pathology departmental database. Cases that were signed out as breast origin given the available immunohistochemical profile and clinical history were included. A tissue microarray was constructed using 1 mm cores in triplicates and studied by immunohistochemistry for AR, ER, PR and HER2 (SP107, SP1, IE2, 4B5; Ventana Medical Systems, Tucson AZ, USA). HER2 gene amplification was determined by INFORM HER2 DNA and Chromosome 17 (both by Ventana Medical Systems, Tucson AZ, USA). Immunohistochemistry was used as a surrogate to determine intrinsic subtypes. RESULTS Among 61 breast cancer BrM with available tissue blocks, AR was expressed in 38 (62%) cases. Among BrMs of luminal A subtype (ER+, PR+/-, HER2-, Ki67<16%), 50% expressed AR (n=1/2). Within the luminal B subtype (ER+, PR+/-), all 15 HER2+ BrM expressed AR (100%), while only 50% of HER2- BrM expressed AR (n=8/16). Among 14 BrM of HER2+ subtype (ER-, PR-), 71% expressed AR (n=10/14). Only 30% of triple negative BrM (ER-, PR-, HER2-) were AR+ (n=4/14). CONCLUSION Almost two-thirds of breast cancer BrM expressed AR. HER2+ luminal B and HER2+ subtypes were most likely to be AR+, while only 30% of triple negative BrM were AR+. Our data suggests that certain subtypes of breast cancer BrM are more likely to be AR+ and could serve as a potential therapeutic target.
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Onishi, Ryo, Kaoru Sato, Kensaku Murano, Lumi Negishi, Haruhiko Siomi, and Mikiko C. Siomi. "Piwi suppresses transcription of Brahma-dependent transposons via Maelstrom in ovarian somatic cells." Science Advances 6, no. 50 (December 2020): eaaz7420. http://dx.doi.org/10.1126/sciadv.aaz7420.
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Drosophila Piwi associates with PIWI-interacting RNAs (piRNAs) and represses transposons transcriptionally through heterochromatinization; however, this process is poorly understood. Here, we identify Brahma (Brm), the core adenosine triphosphatase of the SWI/SNF chromatin remodeling complex, as a new Piwi interactor, and show Brm involvement in activating transcription of Piwi-targeted transposons before silencing. Bioinformatic analyses indicated that Piwi, once bound to target RNAs, reduced the occupancies of SWI/SNF and RNA polymerase II (Pol II) on target loci, abrogating transcription. Artificial piRNA-driven targeting of Piwi to RNA transcripts enhanced repression of Brm-dependent reporters compared with Brm-independent reporters. This was dependent on Piwi cofactors, Gtsf1/Asterix (Gtsf1), Panoramix/Silencio (Panx), and Maelstrom (Mael), but not Eggless/dSetdb (Egg)–mediated H3K9me3 deposition. The λN-box B–mediated tethering of Mael to reporters repressed Brm-dependent genes in the absence of Piwi, Panx, and Gtsf1. We propose that Piwi, via Mael, can rapidly suppress transcription of Brm-dependent genes to facilitate heterochromatin formation.
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Yang, Shao-Ping, Yimin Duan, Xiangliang Yuan, Lin Zhang, Patrick Zhang, Jason T. Huse, and Dihua Yu. "Abstract 4176: Histone deacetylase inhibitor Panobinostat enhances efficacy of immune checkpoint inhibitor via upregulating antigen presentation in breast cancer brain metastasis." Cancer Research 82, no. 12_Supplement (June 15, 2022): 4176. http://dx.doi.org/10.1158/1538-7445.am2022-4176.
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Abstract Brain metastasis (BrM) affects millions of cancer patients and major cancer types, e.g., lung cancer, melanoma, and breast cancer, have high incidences of BrM. Symptomatic BrM patients have a less than 20% 1-year survival rate. The poor clinical outcome is due to lack of effective treatment for BrM as even immune checkpoint inhibition (ICI) only showed effects in 55% asymptomatic BrM in melanoma patients. Novel effective combination therapies are urgently needed to address metastasis in the unique brain immune microenvironment (BrIME). Interestingly, our RNA-seq data of patients treated at MD Anderson Cancer Center and immunohistochemistry (IHC) analysis of tumors of various mouse models showed that BrM express significantly lower major histocompatibility class I (MHC-I) and higher histone deacetylase (HDAC) 1 compares to extracranial tumors or metastasis. HDAC inhibitors (HDACi) have been reported to upregulate MHC-I in extracranial tumors. In this study, we tested whether HDACi, Panobinostat, can upregulate MHC-I expression in BrM and whether Panobinostat combined with ICI (e.g., anti-PD1) treatment in mouse models can impede BrM development. Clearly, our data showed that HDACi Panobinostat significantly increased MHC-I expression in brain-seeking human breast cancer cells (MDA-231, MDA-435) and mouse mammary tumor cells (4T1, EO771) with or without IFN-γ treatment. We then tested Panobinostat penetration of the blood-brain barrier (BBB) for treating BrM in vivo. C57BL/6 mice were treated with either 10 or 20mpk (i.p.) Panobinostat for three consecutive days. Mass spectrum analysis shows that Panobinostat can be detected in the brain at level of 10-8M after the treatment. We found that Panobinostat treatment increased both CD4+ and CD8+ T cell in the brain by FACS analysis. To test therapeutic efficacy of HDACi and ICI combination therapy in BrM, we induced BrM in C57BL/6 mice by intracarotid artery (ICA) injection of E0771-Luc.GFP tumor cells, then mice were divided to four groups and were treated with i) vehicle, ii) Panobinostat, iii) anti-PD1 and iv) Panobinostat +anti-PD1. We found that combination of Panobinostat with anti-PD1 more effectively inhibited BrM tumor outgrowth compares to either monotherapy and the vehicle control. Furthermore, Immunohistochemistry staining revealed upregulated MHC-I in BrM tumor cells and increased CD8+ T cell infiltration by Panobinostat treatment. In summary, our data indicated that HDACi Panobinostat can increase ICI efficacy in BrM by upregulating MHC-I for enhanced antigen presentation. Citation Format: Shao-Ping Yang, Yimin Duan, Xiangliang Yuan, Lin Zhang, Patrick Zhang, Jason T. Huse, Dihua Yu. Histone deacetylase inhibitor Panobinostat enhances efficacy of immune checkpoint inhibitor via upregulating antigen presentation in breast cancer brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4176.
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Aznan, Mohamad Faisal Ni, NAZLINA HAIZA MOHD YASIN, Norzila Mohd, and Mohd Sobri Takriff. "Growth Kinetics Determination Using Different Mathematical Models for Microalgae Characium sp. UKM1, Chlorella sp. UKM2 and Coelastrella sp. UKM4." ASM Science Journal 17 (July 5, 2022): 1–12. http://dx.doi.org/10.32802/asmscj.2022.930.
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Microalgae are extensively used in industry due to their potential in producing high-value metabolites. The good microalgae growth kinetics performance is essential owing to excellent microalgae biomass harvesting efficiency. Therefore, the best mathematical model for the growth kinetics of microalgae is required to predict the correct growth kinetics value and helps in the elucidation of downstream processes. This study embarks on the objective to determine the best mathematical models for three local microalgae which are Characium sp. UKM1, Chlorella sp. UKM2 and Coelastrella sp. UKM4 cultured in Bold Basal Media (BBM). The four mathematical models are used to evaluate the growth kinetics of microalgae which include logistic model (Lm), modified logistic model (MLm), modified Gompertz model (MGm) and Baranyi-Roberts model (BRm). The experimental data were compared to the predicted data through the residual plot. The comparison shows that BRm is the best model to fit UKM1, UKM2 and UKM4 due to the experimental data which is close to the x-axis of the residual plot indicating the data were fitted the best to the BRm. The statistical analysis confirmed that all microalgae growth patterns exhibited that the BRm is the best model owing to the lowest percentage of standard error prediction indicating the lowest error compared to the other models. In addition, accuracy and bias factors are near to one which assess the precision of these models. In conclusion, the growth of UKM1, UKM2 and UKM4 grown in BBM is best fitted to the Baranyi-Roberts model.
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Dankner, Matthew, Sarah M. Maritan, Neibla Priego, Javad Nadaf, Andy Nkili, Rebecca Zhuang, Georgia Kruck, et al. "Abstract 1569: pSTAT3+ stromal cells drive the invasive growth of brain metastases." Cancer Research 82, no. 12_Supplement (June 15, 2022): 1569. http://dx.doi.org/10.1158/1538-7445.am2022-1569.
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Abstract Background: Brain metastases (BrM) with highly invasive (HI) growth patterns are associated with shortened local recurrence free- and overall survival compared to minimally invasive (MI) lesions (Dankner et al. 2021). Compared to MI lesions, HI BrM form abundant contacts with cells in the peritumoral brain, particularly GFAP+ reactive astrocytes (RAs). RAs expressing phosphorylated STAT3 (pSTAT3+ GFAP+ cells) have been shown to be required for BrM colonization and outgrowth (Priego et al. 2018). Here, we investigate the role of pSTAT3+ cells in the brain microenvironment in promoting invasive growth. Methods: We performed immunohistochemistry to identify pSTAT3+ GFAP+ cells in HI and MI human and patient-derived xenograft BrM. We assessed how pharmacological inhibition or genetic ablation of STAT3 affected HI and MI BrM growth in vivo with patient-derived xenograft and syngeneic models of BrM. The secretome of STAT3+ RAs was interrogated to identify STAT3 target genes that could drive invasive cancer growth. scRNA-Seq from patients with highly invasive brain metastases was used to examine the expression of candidate invasion factors in distinct cell types within the brain. Finally, cancer cell invasion was modeled in vitro using a brain slice-tumor co-culture assay. Results: HI BrM displayed increased pSTAT3+GFAP+ cells compared to MI lesions. Pharmacological STAT3i with Legasil (Silibinin) or genetic ablation of STAT3 specifically in RAs decreased in vivo growth of HI, but not MI, BrM. Brain slice cultures treated with STAT3-activating cytokines induced cancer cell invasion, a response that was ablated with STAT3i. Chi3L1 was identified as a STAT3 target gene expressed abundantly by stromal cells in the BrM microenvironment. Cancer cells treated with recombinant Chi3L1 showed enhanced invasion into brain slice cultures compared to control-treated cells. Conclusions: pSTAT3+GFAP+ cells are over-represented in HI BrM, rendering HI BrM preferentially sensitive to STAT3i. pSTAT3+ stromal cells functionally contribute to BrM invasion within the brain, in part through Chi3L1. This work nominates HI histopathological growth pattern as a predictive biomarker of response to STAT3i, and highlights Chi3L1 as a novel therapeutic target for the management of HI BrM. Citation Format: Matthew Dankner, Sarah M. Maritan, Neibla Priego, Javad Nadaf, Andy Nkili, Rebecca Zhuang, Georgia Kruck, Dongmei Zuo, Alexander Nowakowski, Yanis Inglebert, Paul Savage, Morag Park, Marie-Christine Guiot, Anne McKinney, William J. Muller, Manuel Valiente, Kevin Petrecca, Peter M. Siegel. pSTAT3+ stromal cells drive the invasive growth of brain metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1569.
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Rezende, Cássia Cristina, Laylla Luanna de Mello Frasca, Mariana Aguiar Silva, Rafael Augusto Corrêa Pires, Anna Cristina Lanna, Marta Cristina Corsi de Filippi, and Adriano Stephan Nascente. "Physiological and agronomic characteristics of the common bean as affected by multifunctional microorganisms." Semina: Ciências Agrárias 42, no. 2 (February 24, 2021): 599–618. http://dx.doi.org/10.5433/1679-0359.2021v42n2p599.
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Multifunctional microorganisms (MMs) can have beneficial effects on plants through direct and indirect mechanisms. This study aimed to determine the effect of MMs on shoot and root biomass production; gas exchange; content of macronutrients in the shoots, roots and grains; yield components; and grain yield of common bean plants. A completely randomized design with twenty-six treatments and three replications was used under controlled conditions. Treatments consisted of the application of MMs and their combinations in pairs, with the nine rhizobacteria isolates BRM 32109, BRM 32110 and 1301 (Bacillus sp.), BRM 32111 and BRM 32112 (Pseudomonas sp.), BRM 32113 (Burkholderia sp.), BRM 32114 (Serratia sp.), 1381 (Azospirillum sp.) and Ab-V5 (Azospirillum brasilense); an edaphic fungal isolate T-26 (Trichoderma koningiopsis); and a control (without MMs). These MMs were applied at three time points: microbiolization of the seeds, watering the soil seven days after sowing (DAS) and spraying the plants with 21 DAS. In comparison to the control plants, the isolates 1301 and T-26, in addition to the combinations Ab-V5 + T-26, BRM 32114 + BRM 32110 and 1381 + T-26, provided better results, with an increase of 36.5% in the grain yield, a higher accumulation of biomass (78.0%) and a higher content of N, P and K (42.6, 67.8 and 25.7%, respectively) in the shoots of common bean plants. Therefore, the results allow us to infer that the use of MMs is a good strategy for increasing common bean grain yields.
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Kluger, Harriet M., Peter Forsyth, Nikhil Khushalani, Zeynep Eroglu, Mario Sznol, Thuy Tran, Lucia Jilaveanu, et al. "RBTT-07. A PHASE 2 TRIAL OF PEMBROLIZUMAB AND BEVACIZUMAB IN MELANOMA BRAIN MET PATIENTS." Neuro-Oncology 21, Supplement_6 (November 2019): vi220. http://dx.doi.org/10.1093/neuonc/noz175.919.
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Abstract BACKGROUND Pembro monotherapy (NCT02085070) produces responses in 26% of (mel) BrM pts. VEGF inhibitors (VEGFi) enhance anti-PD-1 activity in preclinicals. Therefore, we initiated a phase 2 study (NCT02681549) of pembro plus bev in BrM pts. METHODS Eligibility includes advanced mel, > 1 asymptomatic BrM, diameter 5-20mm, no steroids, no prior PD-1/PD-L1 or VEGFi. Pembro IV 200mg q3 wks for < yrs with bev 7.5mg/kg for the first 4 cycles. Primary endpoint was BrM RR by modified RECIST. RESULTS Between 8/2016 - 1/2019, 20 mel pts were enrolled. 60% were male mdn age 62;ECOG PS was 0 in 16 and 1 in 4 pts; LDH > ULN in 20%; 4 (20%); 10 were BRAFmt; 8 pts (40%) had > 4 untreated BrM. 12 had a BrM response (7 CR, 5 PR); 1 each with SD, unevaluable and an unconfirmed PR, for an ORR BrM of 60% (12/20). All responses lasted 7+ to 30+ mths. 16 pts are alive. AEs attributable to bev include hypertension, microscopic diverticular perforation and wound dehiscence (1 pt each, all resolved). 1 had mucositis attributed to Pembro. Three d/c’d treatment for grade 3 ALT elevation. Cerebral edema decreased in all pts with baseline edema. CONCLUSIONS Pembro plus bev demonstrates promising activity in melanoma BrMs compared to pembro alone. The pre-specified primary endpoint (> 4 BrM responses/20) was met, supporting further study. The toxicity profile was similar to pembro alone.
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Tsai, Charlton, Bastien Nguyen, Anisha Luthra, Joanne F. Chou, Laura H. Tang, Vivian E. Strong, Daniela Molena, et al. "Brain metastasis in gastroesophageal adenocarcinoma: Outcomes and molecular features." Journal of Clinical Oncology 40, no. 4_suppl (February 1, 2022): 347. http://dx.doi.org/10.1200/jco.2022.40.4_suppl.347.
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347 Background: Brain metastases (BrM) rarely occur in patients with metastatic gastroesophageal adenocarcinoma (GEA) and represent a unique therapeutic challenge. We describe the unique clinical, molecular, and genomic factors associated with mGEA cancer and BrM development in order to help guide future clinical management. Methods: Patients (pts) with GEA seen at Memorial Sloan Kettering Cancer Center (MSKCC) from 2008-2019 and who had consented for genomic tumor profiling with MSK-IMPACT, a capture-based next-generation sequencing platform that detects mutations, copy-number variations, and select fusions, were retrospectively identified. Clinical and pathologic characteristics were reviewed. BrM were identified via International Classification of Diseases (ICD) billing codes and electronic medical record problem lists, and then manually validated. Survival was calculated from the time of BrM diagnosis until date of death or last follow up and estimated using the Kaplan-Meier method. Results: Fifty pts with GEA metastatic to the brain were identified. Most pts were male (86%) and white (80%), with primary tumor of the esophagus/gastroesophageal junction (82%) and intestinal-type Lauren histology (90%). Twenty-three pts (46%) were HER2 positive (defined as IHC 2+/FISH+ or IHC 3+). Frequencies of PTEN (16%) and EGFR (22%) alterations in primary or metastatic sites were enriched in pts with BM compared to that seen across the MSKCC retrospective cohort and the GEA Cancer Genome Atlas (TCGA) cohort. The majority (68%) of pts had stage IV disease at initial diagnosis, and 4 pts were found to have BrM within 1 month (mo) of stage IV diagnosis, while 27 pts developed BrM during therapy. Median time to BrM diagnosis was 18.3 mos (IQR 11.5-28.9) and 15.1 mos from stage IV diagnosis (IQR 4.8-25.5). Median survival was 7.6 mos from BrM diagnosis and 15.6 (95% CI 10.0-NR, n = 19), 7.6 (95% CI 2.5-NR, n = 13), and 4.3 (95% CI 3.5-12.3, n = 18) mos for pts with 1, 2-3, or 4+ BrM, respectively. Conclusions: GEA pts with BrM had increased frequency of HER2 positivity, as well as PTEN and EGFR alterations, compared to GEA pts overall historically. Further correlation between BrM development, molecular characteristics, and survival in a larger cohort will be presented.
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TOKUNAGA, Tohru. "BRM. From the viewpoint of basic medicine." Skin Cancer 4, no. 2 (1989): 341–48. http://dx.doi.org/10.5227/skincancer.4.341.
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Stanimirov, Pavel, and Milena Petkova. "BISPHOSPHONATE - RELATED MUCOSITIS (BRM): A CASE REPORT." Journal of IMAB - Annual Proceeding (Scientific Papers) 23, no. 1 (March 14, 2017): 1487–89. http://dx.doi.org/10.5272/jimab.2017231.1487.
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Nakagami, Yoshizo, Yasunori Hiraoka, Tsawtung Lin, and Hiroyuki Abe. "Clinical application of BRM on cancer treatments." Journal of Nippon Medical School 52, no. 5 (1985): 598–601. http://dx.doi.org/10.1272/jnms1923.52.598.
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Coisy-Quivy, Marjorie, Olivier Disson, Virginie Roure, Christian Muchardt, Jean-Marie Blanchard, and Jean-Christophe Dantonel. "Role for Brm in Cell Growth Control." Cancer Research 66, no. 10 (May 15, 2006): 5069–76. http://dx.doi.org/10.1158/0008-5472.can-05-0596.
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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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Segedi, Maja, Laura N. Anderson, Osvaldo Espin-Garcia, Ayelet Borgida, Teresa Bianco, Dangxiao Cheng, Zhuo Chen, et al. "BRM polymorphisms, pancreatic cancer risk and survival." International Journal of Cancer 139, no. 11 (August 18, 2016): 2474–81. http://dx.doi.org/10.1002/ijc.30369.
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Marquez-Vilendrer, Stefanie B., Sudhir K. Rai, Sarah JB Gramling, Li Lu, and David N. Reisman. "BRG1 and BRM loss selectively impacts RB and P53, respectively: BRG1 and BRM have differential functions in vivo." Oncoscience 3, no. 11-12 (December 21, 2016): 337–50. http://dx.doi.org/10.18632/oncoscience.333.
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Liu, G., S. Gramling, D. Munoz, D. Cheng, A. K. Azad, M. Mirshams, Z. Chen, et al. "Two novel BRM insertion promoter sequence variants are associated with loss of BRM expression and lung cancer risk." Oncogene 30, no. 29 (April 11, 2011): 3295–304. http://dx.doi.org/10.1038/onc.2011.81.
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