106,784 research outputs found
Amira Saed; Ishag Adam; Salah Eldin G. Elzaki; Hiba A. Awooda; Hamdan Zaki Hamdan :Leptin receptor gene polymorphisms c.668A>G and c.1968G>C in Sudanese women with preeclampsia: a case-control study Data set
No full textLeptin receptor gene polymorphisms c.668A>G and c.1968G>C in Sudanese women with preeclampsia: a case-control stud
Abstract 2922: The utility of BET inhibition in the sensitization and re-sensitization of pancreatic cancer cells to paclitaxel
No full textAbstract While the mortality rates of cancer are generally declining, pancreatic cancer persists to be an exception with a 5-year-survival rate of less than 7%. As late diagnosis and resistance to conventional therapies are major contributors to high mortality rates, novel treatment options are needed to improve the prognosis of pancreatic cancer patients. Recent findings showed that inhibition of the Bromodomain and Extraterminal Domain (BET) family of epigenetic reader proteins is effective, both alone and in combination with conventional chemotherapy, in decreasing pancreatic tumor growth in patient-derived xenografts. Thus, we aim to evaluate the potential role of and mechanisms of action of BET inhibitors (BETi) as an adjuvant therapy option in pancreatic ductal adenocarcinoma. We established L3.6 pancreatic cells that are resistant to paclitaxel by maintaining them in incrementally higher concentrations for 3 months. Paclitaxel-resistant cells showed a half maximal inhibitory concentration (IC50) 100-fold higher than that of parental cells. Intriguingly, we report that low, non-cytostatic concentrations of the BETi, JQ1, not only sensitized cells to paclitaxel, but also induced significant re-sensitization of chemoresistant cells. In order to elucidate the mechanism by which BETi induces chemo-sensitization, we investigated the differential gene expression profiles of resistant and sensitive cells. Thereby, we uncovered that BETi reverses the regulation of transcriptionally-activated genes in resistant cells. Interestingly, these genes showed a major tendency to gain BRD4 at putative enhancer regions. We anticipate that enhancer RNAs (eRNAs) transcribed at these particular enhancers may provide us with novel biomarkers which can be used to predict chemotherapeutic resistance and the possibility of re-sensitization by BETi. In conclusion, we provide evidence that BETi can potentially be used as adjuvant agents in pancreatic cancer. However, approaches may likely be largely independent of their anti-proliferative effects that require higher concentrations and possibly lead to intolerable adverse effects, but rather to their transcriptional regulatory functions that attenuate the activated programs in chemoresistant cancers. Citation Format: Feda H. Hamdan, Ana P. Kutschat, Madhobi Sen, Xin Wang, Steven A. Johnsen. The utility of BET inhibition in the sensitization and re-sensitization of pancreatic cancer cells to paclitaxel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2922
Abstract 3936: Bromodomain testis-specific protein BRDT is expressed in a subset of esophageal squamous cell carcinomas and controls expression of differentiation-associated genes
No full textAbstract Esophageal cancer is one of the most malignant cancers, ranking as the sixth leading cause of cancer-related deaths worldwide. The poor survival rate and prognosis highlight the limitations in the biological understanding of esophageal cancer and the urgent need for identification of novel targeted molecular therapies. Recently, large scale genomic analyses have revealed the extensive alternations of epigenetic regulators which may be used as a basis for developing new “epigenetic drugs “. BRDT, bromodomain testis-specific protein, is a member of the bromodomain and extra-terminal (BET) family of epigenetic reader proteins. BET proteins can regulate gene expression by recognizing acetylated lysines, thus playing important roles in both normal development and disease progression. Inhibition of BET proteins has emerged as a potential therapy for many types of cancer. In normal human tissues, unlike the other members of BET family, BRDT is exclusively highly expressed in testes where it drives the meiotic and post-meiotic gene expression to promote spermatogenesis. We have identified BRDT to be expressed in over 20% of esophageal squamous cell carcinoma (ESCC), a predominant subtype of esophageal cancer. Knockdown of BRDT does not affect cell proliferation, but leads to alterations in the expression of differentiation markers. In addition, RNA-seq following BRDT knockdown also supports a role of BRDT in cell differentiation. Depletion of BRDT does not alter the cellular response to BET inhibition. Surprisingly, we also identified BRDT transcripts encoding two truncated isoforms lacking the first bromodomain, which could potentially alter its epigenetic reader function. The genome occupancy profile of BRDT showed a significant enrichment at transcription start site (TSS), which is distinct from BRD4. It also showed potential interactions between BRDT and E2F family and SMAD family. Together, we showed that BRDT is overexpressed in ESCC cell lines and may influence ESCC development or progression in a subset of tumors by regulating cell differentiation-associated genes. Citation Format: Xin Wang, Feda H. Hamdan, Madhobi Sen, Ana P. Kutschat, Steven A. Johnsen. Bromodomain testis-specific protein BRDT is expressed in a subset of esophageal squamous cell carcinomas and controls expression of differentiation-associated genes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3936
Epigenetic Targeting of Aberrant Transcriptional Modulation in Pancreatic Cancer
No full textWhile the mortality rates of cancer are generally declining, pancreatic cancer persists to be an exception with a 5-year-survival rate of less than 7%. Late diagnosis and resistance to conventional therapies contribute to high mortality rates in spite of the remarkable recent advances in cancer management and research. Consequently, there is an urgent need to find new and unconventional therapeutic targets to improve prognosis and survival of pancreatic cancer patients. In this review, we discuss the transcriptional effects of the most widely used epigenetic inhibitors in pancreatic cancer focusing on Bromodomain and Extraterminal domain (BET) and Histone Deacetylase (HDAC) inhibitors, which are currently highly promising therapeutic options. We suggest that these inhibitors can be better utilized at lower doses which exploit their transcriptional modulatory effects on pancreatic cancer transcriptional programs directed by specific factors such as MYC and Forkhead Box A1 (FOXA1), rather than simply based on their anti-proliferative effects. This approach can potentially help avoid the intolerable adverse events frequently elicited by the use of these treatments at higher doses. In particular, we underscore the crucial role of distal regulatory elements in mediating the specific effects of these epigenetic inhibitors and propose using them in a more selective and prudent manner
The Relationship between Postpartum Depression and Breastfeeding
No full textIntroduction: The purpose was to investigate the possible correlation or predictive relationship between breastfeeding and Postpartum Depression (PPD). Method: We conducted a prospective study in which 137 Arab women were assessed during pregnancy and postpartum. Current breastfeeding was correlated with postpartum outcomes (EPDS and MINI), employment, and use of formula at 2 and 4 months postpartum, as well as with other variables. Results: Women who were breastfeeding at 2 and 4 months had lower scores on EPDS (p 0.0037 and p 0.0001, respectively) and were less likely to be diagnosed with PPD at 4 months (p 0.0025). Higher scores on EPDS and diagnosis of PPD at 2 months were predictive of lower rates of breastfeeding at 4 months (p 0.0001 and p 0.005, respectively). Women who were employed and using formula at 2 months were less likely to breastfeed at 4 months (p 0.0001). Breastfeeding women at 2 months had lower scores on EPDS (p 0.003) and were less likely to be diagnosed with PPD (p 0.05) at 4 months. Discussion: The results indicate that women who breastfeed their infants reduced their risk of developing PPD, with effects being maintained over the first 4 months postpartum. PPD may also decrease the rate of breastfeeding, suggesting a reciprocal relationship between these variables. © 2012 Baywood Publishing Co., Inc.Abou-Saleh MT, 1998, PSYCHONEUROENDOCRINO, V23, P465; Beck CT, 2001, NURS RES, V50, P275, DOI 10.1097-00006199-200109000-00004; McCoy Sarah J Breese, 2006, J Am Osteopath Assoc, V106, P193; Dennis CL, 2009, PEDIATRICS, V123, pE736, DOI 10.1542-peds.2008-1629; Dunn S, 2006, JOGNN-J OBST GYN NEO, V35, P87, DOI 10.1111-J.1552-6909.2006.00005.x; Galler JR, 1999, J DEV BEHAV PEDIATR, V20, P80, DOI 10.1097-00004703-199904000-00002; Ghubash R, 1997, SOC PSYCH PSYCH EPID, V32, P474; Ghusbash R, 2009, PSYCHOL REP, V105, P127; Green Katherine, 2006, Psychol Health Med, V11, P425, DOI 10.1080-13548500600678164; Hamdan A, 2011, ARCH WOMEN MENT HLTH, V14, P125, DOI 10.1007-s00737-010-0189-8; Hatton DC, 2005, J HUM LACT, V21, P444, DOI 10.1177-0890334405280947; Ip S, 2009, BREASTFEED MED, V4, pS17, DOI 10.1089-bfm.2009.0050; Kavanaugh K, 1997, J Hum Lact, V13, P15, DOI 10.1177-089033449701300111; Kehler HL, 2009, CAN J PUBLIC HEALTH, V100, P376; Kelly YJ, 2005, PUBLIC HEALTH NUTR, V8, P417, DOI 10.1079-PHN2004702; Kendall-Tackett Kathleen, 2007, Int Breastfeed J, V2, P6, DOI 10.1186-1746-4358-2-6; Kimbro RT, 2006, MATERN CHILD HLTH J, V10, P19, DOI 10.1007-s10995-005-0058-7; Labbok MH, 2001, PEDIATR CLIN N AM, V48, P143, DOI 10.1016-S0031-3955(05)70290-X; Lecrubier Y, 1998, EUR PSYCHIAT, V13, P198, DOI 10.1016-S0924-9338(98)80004-7; LOCKLIN MP, 1993, BIRTH-ISS PERINAT C, V20, P30, DOI 10.1111-j.1523-536X.1993.tb00176.x; OHara MW, 1996, INT REV PSYCHIATR, V8, P37, DOI 10.3109-09540269609037816; Robertson E, 2004, GEN HOSP PSYCHIAT, V26, P289, DOI 10.1016-j.genhosppsych.2004.02.006; Sheehan DV, 1998, J CLIN PSYCHIAT, V59, P22, DOI 10.4088-JCP.09m05305whi; Stewart DE, 2003, POSTPARTUM DEPRESSIO; SUSMAN VL, 1988, AM J PSYCHIAT, V145, P498; Taveras EM, 2003, PEDIATRICS, V112, P108, DOI 10.1542-peds.112.1.108; Vogel A, 1999, ACTA PAEDIATR, V88, P1320, DOI 10.1080-08035259975003001321
DeltaNp63-dependent super enhancers define molecular identity in pancreatic cancer by an interconnected transcription factor network
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Abstract 1472: The role of the BAF complex in Wnt signaling-mediated transcriptional regulation in colorectal cancer
No full textAbstract Recent genome- and exome-wide sequencing studies have revealed a close association between the epigenome and the pathogenesis of cancer. Not only were chromatin regulators found to be commonly mutated in a wide range of cancers, but a class of these regulators, the ATP-dependent chromatin remodelers, especially subunits of the mammalian BAF complex, were among the most frequently mutated group of genes across cancer types, mutated in over 20% of cancers. Among these subunits, loss of function mutations in ARID1A (AT-rich interactive domain-containing protein 1A) are most frequent across cancer types including 10% of colorectal cancer (CRC). Very interestingly, a recent publication described the pivotal role of the loss of ARID1A in driving CRC wherein its inactivation alone led to the formation of invasive adenocarcinomas in mice. However, surprisingly, in contrast to the expected tumor suppressive role of ARID1A in CRC, we observe that the knockout (KO) of ARID1A in CRC cell lines leads to impaired proliferation. Moreover, subcutaneous xenografts in SCID/SHO mice using ARID1A KO CRC cells did not form more aggressive tumors than their wild type counterparts. One of the most commonly occurring mutations in CRC is in the APC gene, which leads to hyperactive Wnt signaling. Thus CRC progression is typically highly dependent on this pathway. Notably, it is reported that loss of ARID1A in the context of APC mutations results in diminished tumor formation in mice and increased differentiation. This led us to hypothesize that ARID1A is required for Wnt signaling-mediated transcriptional (de)regulation in CRC. To uncover this further, we utilized several publically available ChIP-seq, RNA-seq and ATAC-seq datasets as well as our own ChIP-seq data for ARID1A in the HCT116 cell line. We observe a substantial co-localization of the BAF complex with TCF7L2, a downstream effector of the Wnt signaling pathway, suggesting cooperation between these factors. Further, these sites are also co-occupied by AP1 transcription factors. A crosstalk between the TCF7L2 and AP1 factors has been reported in intestinal tumors. From data available in the ARID1A KO system, we observe a downregulation of potential target genes which are co-occupied at neighboring sites by these factors. Therefore, we suggest that ARID1A plays an important role in the regulation of colorectal cancer relevant genes that are targets of TCF7L2/AP1, thus facilitating a pathway that is most commonly hijacked in colorectal cancer. Citation Format: Madhobi Sen, Feda H. Hamdan, Xin Wang, Jacobe Rapp, Steven A. Johnsen. The role of the BAF complex in Wnt signaling-mediated transcriptional regulation in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1472
Toleranz oder Anerkennung?
No full textDiehm I. Toleranz oder Anerkennung? In: Burk K-H, Speck-Hamdan A, Wedekind H, eds. Kinder beteiligen - Demokratie lernen?. Frankfurt a.M.: Grundschulverband; 2003: 325-335
Nilai-Nilai Adab Seorang Pendidik Menurut Buku Kepribadian Pendidik Dalam Al-Qur’an Karya Hifza Hamdan
No full textThis research is motivated by the book Personality of Educators in the Qur'an by Hifza Hamdan which offers the concept of education and the personality of an educator, as well as its relevance to the reality of education today, is a form of scientific endeavor that can be expected to have many values, one of which is related to education adab. The purpose of this study is to describe and analyze: 1) Adab values that must be possessed by an educator in the book Personality of Educators in the Qur'an by Hifza Hamdan. 2) Implementation of the educational values of an educator in the Personality of Educators in the Qur'an by Hifza Hamdan. This study uses a qualitative approach with the type of literature study (library research). The data source used in this study is the text in the book Personality of Educators in the Al-Qur'an Its Relevance to Contemporary Reality by Hifza Hamdan, then the data collection technique uses document analysis. The data analysis technique used is content analysis. Based on the results of the analysis carried out, the results of this study are: 1) The values of etiquette that must be possessed by an educator in the book Personality of Educators in the Al-Qur'an by Hifza Hamdan, are as follows: a) Have wisdom; (honest, consistent (istiqomah), intelligent (fatanah), trustworthy (amanah) and convey (tabligh), b) Sincerity c) Humble d) Learner, e) Tolerant and appreciative, f) Compassionate and compassionate, g) Wise , h) Generous and commendable, i) Forgiving and forgiving, j) Speaks kind words and touches the soul, k) Patient and steadfast, l) Creative and innovative, m) Dignified and charismatic, n) Devotion spirit, o), Capable set an example. 2) Implementation of the Adab Values of an Educator in the Personality of Educators in the Al-Qur'an by Hifza Hamdan, namely as educators as caregivers, educators-educators, educators as caregivers, educators as guides (givers of instructions), educators as protectors, educators as teachers and educators as experts in science
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