Literatura científica selecionada sobre o tema "Philadelphia Normal School"

Abstract Leukemia, a cancer impacting blood-forming tissues such as bone marrow and the lymphatic system, presents in various forms, affecting children and adults differently. The therapeutic approach is complex and depends on the specific leukemia type. Effective management is crucial as it disrupts normal blood cell production, increasing infection susceptibility. Treatments like chemotherapy can further weaken immunity. Thus, a patient’s healthcare plan should focus on comfort, reducing chemotherapy side effects, protecting veins, addressing complications, and offering educational and emotional support. One of the greatest challenges we face in cancer research and treatment is the ability of cancer to adapt, evolve, and become drug-resistant. We expect that the future of cancer treatment will be in combining therapies to overcome resistance – but we need to get much better at predicting which drug combinations will work best for individual patients. Recent studies showed that a combination of two drugs keeps patients with chronic lymphocytic leukemia disease-free and alive longer than the current standard of care, according to the Stanford University School of Medicine and multiple other institutions. This article proposes studies on the combined use of drugs for treating leukemia. Employing a mix of medicines might decrease the chances of tumor resistance. Starting multiple drugs concurrently allows for immediate application during disease onset, avoiding delays. Initial chemotherapy uses a drug combination to eliminate maximum leukemia cells and restore normal blood counts. Afterward, intensification chemotherapy targets any residual, undetectable leukemia cells in the blood or bone marrow. To recommend a drug combination to treat/manage Leukemia, we have employed a Graph Neural Network to pass information between these trending drugs and genes that act as potential targets for Leukemia. Citation Format: Archishma Marrapu. Graph-Based Deep Learning for Predicting Synergy in Multi-Drug Treatments for Leukemia [abstract]. In: Proceedings of the Blood Cancer Discovery Symposium; 2024 Mar 4-6; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(2_Suppl):Abstract nr P31.

Abstract Marvel D3 and its associated junctional proteins in breast cancer Wenxiao Ji, Wen G. Jiang, Tracey A. Martin CCMRC, Cardiff University School of Medicine, Cardiff, Wales, UK Introduction. Marvel (Membrane Associated Domain Containing) proteins are a small family of proteins that are concentrated at the tight junction (TJ) region of epithelial and endothelial cells. They are important players in the formation and regulation of TJs. The Marvel protein family has three members, Marvel-D1, Marvel-D2 and Marvel-D3, all known to be TJ components. Marvel-D3 is more prominent in TJ regulation, by interacting widely with other proteins that co-localised at TJs. In the present study, we have examined the expression of Marvel-D3 and its splicing variants, their relationship with other known interactive TJ partners in breast cancer and in disease progression and clinical outcome. Methods. Marvel-D3 and its variants were quantified in a breast cancer cohort that contained both normal and tumour tissues. The expression was analysed together with the known Marvel-D3 interactive molecules available in our database of the same cohort. The profile of the expression of the molecules was also integrated to search for a pattern of the expression that may have clinical significance including the survival of the patients. Results. Marvel-D3 had significantly high levels in breast cancer tissues than normal tissues (p=0.011). The difference between normal and tumour tissues for two Marvel-D3 variants were not statistically significant. Of all the known Marvel-D3 interactive proteins that were available for analyses, we identified thirteen with viability in integrated analyses; they include the JAM family members, Marvel-D2, occludin, the zonula occluden family members, small number of the claudin family members and cingulin, all being important TJ components. The integrated expression of these Marvel-D3 partners presented a highly significant predictive power for the overall survival of the patients (RUC=0.821, p< 0.0001). Stratifying the patients based on the profile has a significant value in evaluating survival (survival rate 95.7% with favourable expression versus 57.1% unfavourable, during the followup period). This predictive power is independent of other clinical and hormonal receptor status (p< 0.001, HR=1.226 (95% CI 1.094-1.373)). We have also noted that this predictive value is applicable to subtypes of the breast cancer and hormone receptor status with similar predictive power. Conclusion. Expression of Marvel-D3, a TJ component, together with its interactive TJ partners, including both transmembrane and intracellular subcoat proteins, form an important clinical indicator for clinical progression of breast cancer. Citation Format: WENXIAO JI, Wen G. Jiang, Tracey A. Martin. Marvel D3 and its associated junctional proteins in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-20.

Abstract Introduction: Levonorgestrel-releasing intrauterine system (LNG-IUS) is associated with ~50% risk reduction for uterine cancer incidence and can be an effective primary prevention strategy. We aimed to understand current patterns of LNG-IUS use and identify disparities that could inform implementation strategies for more effective and equitable uterine cancer primary prevention. Methods: We analyzed LNG-IUS use among U.S. women aged 18-50 with the 2017-2019 National Survey of Family Growth. Statistical analysis was stratified by race, sociodemographic, and health factors. Predictors of LNG-IUS use were assessed through weighted multivariable logistic regression using the Wald chi-square test. Results: Current LNG-IUS use was significantly lower in Hispanic women compared to White women (AOR 0.65, P=0.049). Compared to women with up to a high school education, LNG-IUS use was higher for women with a college degree or higher in the overall sample (AOR 1.86, P=0.009), White women (AOR 1.91, P=0.04), and Black women (AOR 4.54, P=0.007), but not for Hispanic women (AOR 0.79, P=0.64). All racial/ethnic subgroups had lower odds of LNG-IUS for non-parous women than parous women (all P<0.002). Although a known uterine cancer risk factor, obesity was not associated with LNG-IUS use. Conclusions: Hispanic women, women with lower educational levels, and nulliparous women have disproportionately low LNG-IUS use despite being at increased uterine cancer risk. Community-based educational interventions for high-risk women and their providers on the benefits of LNG-IUS on uterine cancer prevention are needed to mitigate uterine cancer disparities. Table 1. Logistic Regression on Predictors for LNG-IUS Use in U.S. Women Aged 18-50 OVERALL (N=4107) WHITE (n=1948) HISPANIC (n=1052) BLACK (n=861) AOR (95% CI) AOR (95% CI) AOR (95% CI) AOR (95% CI) Race Ref 0.65* (0.42-0.98) 0.77 (0.46-1.27) Age 18-24 1.16 (0.55-2.46) 1.15 (0.45-2.94) 13.13* (1.42-121.3) 0.55 (0.11-2.83) 25-34 1.65 (0.88-3.10) 1.46 (0.69-3.13) 31.75** (4.04-249.5) 0.63 (0.18-2.14) 35-44 1.07 (0.55-2.10) 1.10 (0.49-2.47) 13.28* (1.51-116.6) 0.54 (0.14-2.02) 45-50 Ref Ref Ref Ref Education ≤High School Ref Ref Ref Ref Some College 1.56* (1.02-2.51) 1.56 (0.83-2.94) 1.05 (0.47-2.32) 3.90* (1.39-10.96) ≥Bachelor’s 1.86** (1.17-2.97) 1.91* (1.03-3.54) 0.79 (0.30-2.12) 4.54** (1.51-13.65) BMI Normal Ref Ref Ref Ref Overweight 1.44 (0.93-3.22) 1.40 (0.81-2.41) 0.96 (0.35-2.62) 1.54 (0.56-4.22) Obese 0.87 (0.57-1.31) 0.86 (0.52-1.43) 0.68 (0.28-1.63) 1.01 (0.35-2.89) Parity Parous 2.85*** (1.89-4.30) 2.21** (1.33-3.67) 7.30*** (2.61-20.38) 5.38*** (2.27-12.76) Nulliparous Ref Ref Ref Ref Abbreviations: AOR, adjusted odds ratio; BMI, body mass index; CI, confidence interval; Ref, reference group. *P<0.05; ** P<0.01; *** P<0.001 aEarly Menarche <12yo; Normal Menarche 12-14yo; Late Menarche >14yo. Citation Format: Paul G. Yeh, Iakovos Toumazis, Charlotte Sun, Karen Lu, Larissa A. Meyer. Disparities in uptake of levonorgestrel-releasing intrauterine system (LNG-IUS): implications for uterine cancer primary prevention. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5769.

Abstract Introduction: Breast cancer was the top cause of cancer deaths in 2020 with a death toll of 685 000 worldwide. Breast cancer treatments are based on drug specificity for unique receptors on the surface of some breast cancer types, there is a search for alternative treatments that are inclusive of different breast cancer types. Evidence suggests that antioxidants offer a protective effect against certain cancers. Studies on Ipomoea cairica have reported potential anticancer activity, hence this study aimed to assess the antioxidant and antiproliferative potentials of the extracts of Ipomoea cairica on three breast cancer cell lines. Materials and Methods- The study protocol was approved by the University of the Free State Health Sciences Research Ethics Committee (HSREC), with approval number: UFS-HSD2022/0353/2607-0001. Ipomoea cairica stem and leaves were harvested and identified by Prof. H. Baijnath, Department of Conservation Science, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa, with specimen number 29 30 DD housed at the Ward Herbarium. The dried plant was extracted sequentially using organic solvents ranging from non-polar to polar and water. The extracts were filtered and concentrated using a rotary evaporator and then evaporated to dryness/lyophilized. Cells were cultured according to standard established procedure. The extracts were subjected to phytochemical analyses. FRAP, DPPH, and ABTS assays were done to examine antioxidant activity and MTT assays were used to evaluate the antiproliferative/cytotoxicity of the extracts against normal (Vero) and breast cancer cell lines (MCF-7, MDA-MB-231, and 4T1). Results and Discussion- Extracts of Ipomoea cairica possess alkaloids, saponins, phenols, flavonoids, phytosterols, tannins, triterpenoids, and anthraquinones. The results from the DPPH and ABTS assays revealed that the methanol and ethyl acetate fractions had significantly the highest antioxidant potentials while the methanol stem extract exhibited the most significant antioxidant activity in the FRAP assay. The DCM stem extract showed the highest antiproliferative activity against all tested cell lines. Conclusion- Extracts of I. cairica possess significant antioxidant properties and antiproliferative activities against a wide array of breast cancer types including the most challenging triple-negative breast cancer. The plant would make for a strong herbal candidate for adjuvant therapy with breast cancer medication. Citation Format: Ayodeji Mathias Adegoke, Doreen Kulabako Kyagaba, Nomonde Hadebe, Nandi Mabaso, Relebohile Patricia Lefojane, Himansu Baijnath, Oyeronke Adunni Odunola, Mamello Patience Sekhoacha. Antioxidant and antiproliferative activities of Ipomoea cairica extracts on three breast cancer cell lines. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3829.

Abstract Introduction: Breast cancer was the top cause of cancer deaths in 2020 with a death toll of 685 000 worldwide. Breast cancer treatments are based on drug specificity for unique receptors on the surface of some breast cancer types, there is a search for alternative treatments that are inclusive of different breast cancer types. Evidence suggests that antioxidants offer a protective effect against certain cancers. Studies on Ipomoea cairica have reported potential anticancer activity, hence this study aimed to assess the antioxidant and antiproliferative potentials of the extracts of Ipomoea cairica on three breast cancer cell lines. Materials and Methods: The study protocol was approved by the University of the Free State Health Sciences Research Ethics Committee (HSREC), with approval number: UFS-HSD2022/0353/2607-0001. Ipomoea cairica stem and leaves were harvested and identified by Prof. H. Baijnath, Department of Conservation Science, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa, with specimen number 29 30 DD housed at the Ward Herbarium. The dried plant was extracted sequentially using organic solvents ranging from non-polar to polar and water. The extracts were filtered and concentrated using a rotary evaporator and then evaporated to dryness/lyophilized. Cells were cultured according to standard established procedure. The extracts were subjected to phytochemical analyses. FRAP, DPPH, and ABTS assays were done to examine antioxidant activity and MTT assays were used to evaluate the antiproliferative/cytotoxicity of the extracts against normal (Vero) and breast cancer cell lines (MCF-7, MDA-MB-231, and 4T1). Results and Discussion: Extracts of Ipomoea cairica possess alkaloids, saponins, phenols, flavonoids, phytosterols, tannins, triterpenoids, and anthraquinones. The results from the DPPH and ABTS assays revealed that the methanol and ethyl acetate fractions had significantly the highest antioxidant potentials while the methanol stem extract exhibited the most significant antioxidant activity in the FRAP assay. The DCM stem extract showed the highest antiproliferative activity against all tested cell lines. Conclusion: Extracts of I. cairica possess significant antioxidant properties and antiproliferative activities against a wide array of breast cancer types including the most challenging triple-negative breast cancer. The plant would make for a strong herbal candidate for adjuvant therapy with breast cancer medication. Citation Format: Ayodeji Mathias Adegoke, Doreen Kulabako Kyagaba, Nomonde Hadebe, Nandi Mabaso, Relebohile Patricia Lefojane, Himansu Baijnath, Oyeronke Adunni Odunola, Mamello Patience Sekhoacha. Antioxidant and antiproliferative activities of Ipomoea cairica extracts on three breast cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1833.

Abstract Background: Cervical cancer is the second most common cancer in the Caribbean region. It is a major public health challenge despite being preventable via HPV vaccination and Pap testing. Cancer stigma has been shown to serve as a barrier to screening, early diagnosis, and treatment seeking. The stigma associated with cervical cancer hinders progress towards its elimination. The purpose of the study was to assess cancer stigma among a non-patient population of males and females using a culturally trans-created scale in Jamaica, Grenada, and Trinidad and Tobago. Methods: A cross-sectional study was conducted with 1207 participants. The survey was comprised of the adapted Cancer Stigma Scale and included additional questions on cervical cancer knowledge and beliefs. Knowledge and attitudes towards the HPV vaccine were also assessed. The survey was distributed online and, in a paper, based format between October 2022 and March 2023. The data were analyzed using SPSS. Results: Preliminary descriptive statistics found 81% of the respondents were female and 44% had a university level education while 52% had a secondary or trade/technical school level of education. In response to cancer stigma items, age, level of education, gender, and relationship status were significant predictors of cancer stigma (p <0.001). Results shows that almost 1 in 5 indicated a person with cancer is responsible and accountable for their condition. Additionally, 46% responded that getting cancer meant having to mentally prepare for death, and 40% agreed that life is never normal after having cancer. Almost 48% agreed that cancer ruins close relationships, and 29% agreed that cancer ruins a person’s career. Moreover, this endorses that stigma impacts screening, treatment seeking and can lead to social isolation, guilt and blame among persons with abnormal screening and cancer diagnoses. Discussion: These results indicate that cancer is stigmatized in the Caribbean, and it influences screening and care seeking. Our findings suggest the role of stigma must be included in prevention strategies that ought to include broad population education campaigns to reduce stigma towards cervical cancer screening and care seeking- as cervical cancer is highly treatable and even curable when detected at the pre-cancer or early stages. Further, the findings, point to the necessity and urgency of cervical cancer prevention policies to improve screening and vaccination rates to save lives and prevent undue early death of Caribbean women. Citation Format: Diadrey-Anne Sealy, Kamilah Thomas-Purcell, Althea Bailey, Gaole Song, Kimlin Ashing. Cancer stigma and its effect on cervical cancer screening and care seeking in the Caribbean [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C142.

Abstract Background: Previous researches found that false-positive mammogram results during breast cancer screening are related to age, family history of breast cancer, body mass index, and breast density. In Brazil, there is limited data available on possible factors that may influence the sensitivity of mammography and, consequently, the overall quality of the breast cancer screening program. Aims: This study aims to conduct a sensitivity analysis comparing the results of screening mammograms with diagnosis of breast cancer, taking into account factors that could impact this sensitivity. Methods: All mammogram and biopsy results in the state of São Paulo in 2013 were obtained from the Brazilian Breast Cancer Information System (SISMAMA) database. We obtained information on age (< 50, 50-59, 60-69, or 70+ years), type of lesion (solid, cyst, or calcifications), lesion size (< 10mm, 11-20mm, 21-50mm, or >50mm), lesion boundaries (defined or undefined), lesion characteristics (regular or irregular), and breast density (fatty/predominant fatty or dense/predominant dense). In addition, we evaluated the hormonal therapy usage (yes or no), radiotherapy treatment (yes or no), ethnicity (caucasian, asian, or black), education (illiterate, completed elementary school, completed high school, or completed higher education), skin type (retracted, thickened, or normal), and type of mammogram (simple or computerized). Our analysis focused on mammograms classified as BI-RADS 4, BI-RADS 5, and those with inconclusive results, which subsequently led to a biopsy for diagnosis. We conduct statistical analysis using SPSS v.29 software. To assess the agreement between mammograms and biopsy results (sensitivity), we calculated the proportion of true positive results. We compared the sensitivity across different strata of variables using the Chi-Square test and the V-Cramer measure. Results: A total of 6,064 women with BI-RADS 4, BI-RADS 5, or inconclusive mammogram results underwent biopsy procedures for breast cancer diagnosis. Among these cases, 3,414 (56.3%) were false positives, 1,765 (29.1%) were true positives, and 885 (14.6%) were inconclusive results. The sensitivity of mammographic screening was not significantly associated with ethnicity, education, type of mammogram, skin type, or previous radiotherapy. However, a higher proportion of false positive results was linked to high breast density (71.2%), irregular lesions with defined boundaries (87.5%), particularly calcifications (68.7%) smaller than 10 mm (67.5 %). True positive results, on the other hand, were associated with solid (87.1%) and irregular lesions with undefined boundaries (82.1 %), often larger than 50 mm (57.2%) in fatty breasts (82.7%). A notable proportion of inconclusive results was associated with the presence of dense/predominant dense breasts (88.4%) and irregular lesions with undefined boundaries (87%), particularly solid lesions (89.8%) ranging from 21 to 50 mm in size (60.8%). False positive and inconclusive results were more prevalent among women under 50 years old (79.8%) and those using hormonal therapy (54.8%) compared to true positives. This study has certain limitations, including the availability of data related to lesion density and morphology, as well as body mass index in the SISMAMA database, all of which can potentially impact mammography sensitivity. Furthermore, a notable limitation was a substantial number of missing values for ethnicity and education in the SISMAMA dataset. Conclusion: We identified associations between false-positive and inconclusive results on screening mammograms and factors such as age, breast density, lesion size, lesion types, and hormonal therapy. These results provide valuable information about potential factors that may affect the accuracy of mammography interpretations. Therefore, they must be taken into consideration when planning a breast cancer screening program. Citation Format: Alice Câmara, Lise Cury, Victor Filho. Factors Affecting the Mammography Sensitivity and the Quality of the Breast Cancer Screening Program in the State of São Paulo, Brazil [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-29-03.

Abstract Expression of Dual Specific Phosphatase-7 (DUSP7/PYST2) and it’s Connection with Salt Inducible Kinases (SIKs) and Downstream MKKs in breast cancer Wenxiao Ji1, Emily Ling Xin1,2, Lin Ye1, Eleri Davies3, Wen G. Jiang1, Tracey A. Martin1 1CCMRC, Cardiff University School of Medicine, Cardiff, Wales, UK 2Breast Centre, Peking University First Hospital, Xicheng District, Beijing, China 3Wales Breast Centre, University Llandough Hospital, Cardiff CF64 2XX, UK Introduction. DUSP7 is a member of the large Dual specific phosphatase family, able to regulate the phosphorylation of both tyrosine and serine/threonine protein kinases. The role of DUSP7 in cancer is not clear, however, it has been identified as a possible target for therapy in cancers including breast cancer. It has also been reported as having value in prognosis of certain cancers, such as haematological malignancies, breast cancer and certain types of gynaecological cancer. The signalling network for DUSP7 is not fully established but is known to connect to ERKs and MAP2Ks. DUSP7 also appears to be linked with salt inducible kinases (SIKs), a small family of kinases linked with progression and response to therapies in breast cancer. Thus, DUSP7 and salt inducible kinases may interact with each other and with the downstream kinases including MAP2Ks and STK11 to influence the clinical course of breast cancer. The present study explored if the pattern of DUSP7 together with salt inducible kinases and the downstream MKKs in breast cancer. Methods. The expression of DUSP7 was quantified in a cohort of breast cancer tissues (both normal mammary tissues and breast cancer tissues). The expression of the potential downstream kinases including MKK1, MKK2, MKK3, MKK4 and STK11 was also quantified. The expression profile of these molecule, together with the salt inducible kinases reported to be aberrant in our previous studies, were analysed against clinical and outcome information. Results. Breast cancer tissues expressed high levels of DUSP7 compared with normal mammary tissues, although not statistically significant. When we explored the relationship between DUSP7 and other potential related molecules in the database of the cohort, we found a highly significant correlation between DUSP7 and SIK1 (r=0.385, p< 0.001), SIK2 (r=0.590, p< 0.001), but not SIK3 (r=0.158, p>0.05). Together with SIK1 and SIK2 (known to link to drug sensitivity), DUSP7, MKK1 (MAP2K1) and MKK3 (MAP2K3) appear to form a gene signature that is of significant value in predicting the overall survival of the patients (ROC 0.723, p=0.001). This allowed us to significantly distinguish between those with good OS and poor OS (p< 0.001, Hazard Ration (HR) =1.443 (95%CI 1.154-1.804)). Multivariate analysis has shown that this signature is independent in predicting overall survival (p=0.013, HR=1.432). The signature is more significant in predicting OS in ER(-) tumours (p< 0.001) than ER(+) tumours (p=0.61). The same is seen when predicting OS with triple negative breast cancers (TNBC) (p< 0.001) than non-TNBC tumours (p=0.044). The gene signature also predicted disease free outcome (p=0.007, HR=1.266 (95% CI 1.065-1.504)). Conclusion. The dual specific phosphatase DUSP7 together with potentially correlated salt inducible kinases (SIK-1 and SIK-2) and downstream MKKs (MKK-1 and MKK3) have important clinical value in breast cancer. This provides support that DUSP7 may be a valuable therapeutic target in breast cancer. Citation Format: WENXIAO JI, Ling Xin, Eleri Davies, Wen G. Jiang, Lin Ye. Expression of Dual Specific Phosphatase-7 (DUSP7/PYST2) and it’s Connection with Salt Inducible Kinases (SIKs) and Downstream MKKs in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-08-22.

Abstract Epithelial ovarian cancer (OC) is typically diagnosed at a late stage and, despite treatment with cytoreductive surgery and chemotherapy, 70-80% of patients relapse and eventually die due to the disease. Major challenges to improve patient outcomes are to overcome therapy resistance and to individually tailor therapy. Uncovering the molecular drivers of OC, especially in the most common subgroup high-grade serous (HGS), will help develop novel therapeutic strategies to meet these challenges. Using the Cancer Genome Atlas (TCGA) data, we observed that a locus in 3q26.2, near the EVI1 oncogene, was the most significantly amplified region in HGS OC, occurring in more than 80% of those tumors. We validated these findings in an OC dataset from the Hartwig Medical Foundation and in OC cell lines from the DepMap database. Furthermore, HGS OC had the highest mean copy number of the 3q26.2 locus co-occurring with high mean EVI1 expression among all tumor entities in the pan-cancer TCGA dataset. These EVI1 expression levels are significantly higher than in normal fallopian tube, from which HGS OC most likely arises. EVI1 overexpression promotes leukemogenesis in 3q26-rearranged acute myeloid leukemia (AML), as a result of chromosomal translocations that enable hijacking of hyperactive enhancers. Here, we hypothesize that EVI1 also plays a crucial role in OC development, but that its aberrant expression in this disease is driven by the amplification of yet undiscovered regulatory elements near EVI1. We showed that EVI1-positive OC cell lines, of which the majority are HGS, are EVI1-dependent and harbor a ~200 kb amplified region near EVI1. This region interacts with the EVI1 promoter (4C-Seq), is characterized by open chromatin (ATAC-Seq), and shows high levels of H3K27 acetylation (H3K27ac ChIP-Seq), suggesting the presence of an active enhancer. Furthermore, based upon H3K27ac signal, we identified within this region a super-enhancer of approximately 65 kb. In OC cell lines without detectable EVI1 levels or cell lines from other cancer subtypes, such as breast and colon cancer, this location had no active enhancer and did not loop to the EVI1 promoter. Altogether, these data point to the generation of a hyperactive super-enhancer driving EVI1 overexpression in OC. These findings emphasize the importance of epigenetic control in the regulation of EVI1 expression, as previously shown in 3q26-rearranged AML. Since OC tumor cell lines are strongly dependent on EVI1, interference with this super-enhancer, leading to loss of EVI1 expression, could be exploited to inhibit tumor growth. For this purpose, we generated GFP-tagged EVI1 cell line models (e.g. SKOV3), which will be used to discover small molecules to target the activity of this super-enhancer. In conclusion, we discovered a new mechanism of enhancer-mediated overexpression of the EVI1 oncogene as a molecular driver in ovarian cancer, with possible implications for therapy. Citation Format: Leonie Smeenk, Sabrina Kruse, Roger Mulet-Lazaro, Ingrid Boere, John Martens, Stefan Gröschel, Claudia Scholl, Stefan Fröhling, Ruud Delwel. Tumor-specific super-enhancer drives overexpression of EVI1 in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3040.

The first months of human post‐natal life are a crucial period for the development and integration of skull and aerodigestive tract (ADT) structures. Anatomical changes coincident with central and peripheral neural development are essential factors that contribute to the establishment of the infant's coordination of breathing and swallowing. This component of our ongoing research has been to identify an optimum MRI database to assess these changes in a joint collaboration between the Children's Hospital of Philadelphia (CHOP) and the Icahn School of Medicine at Mount Sinai (Institutional Review Board approvals: IRB# 16‐012716, HS#: 15‐00198 and GCO#1: 15‐0529/0001). In our prior studies (Curcio et al. 2014, Meaike et al. 2015, Gupta et al. 2015) we identified key features that may be essential to assess and chart the growth of skull and ADT structures, and to track resultant positional shifts. We initially reviewed a total of 806 medical files and MRI scans obtained between 2013 and 2015 at CHOP. To obtain a sample that was anatomically normal and absent of systemic pathologies possibly interfering with growth and proportions of skull and ADT structures, we conducted a two‐step triage process. First, we reviewed the medical files and applied the following exclusion criteria: infants born under 37 and over 42 weeks of gestational age; born with less than 2.5 and more than 4kg; diagnosed growth disorders; diagnosed syndromes (e.g.: Chiari, 1st and 2nd branchial arch syndromes); head circumference beyond normal limits. We then assessed the remaining images and applied the following exclusion criteria: presence of trauma or conditions that determine anatomic abnormalities in the integrity, size, growth and proportions of craniofacial bones and ADT structures; cleft lip, palate / facial cleft; craniosynostosis, microcephaly, hydrocephaly; brain and/or head and neck mass tumors causing deformities of skull and/or ADT structures. Study sample now comprises 157 infants, 81 females, 75 males, from 0 to 5.07 months of age (average=1.33 months, median=0.87 months), distributed per age group as follows: 0–1month (mo) n=84; 1.1–2mo n=36; 2.1–3mo n=15; 3.1–4mo n=5; 4.1–5mo n=16. Next steps will be to validate a protocol to measure skull and ADT structures in the mid‐sagittal (MS) and in axial planes (AP), with optimal reproducibility and accuracy. Our hypothesis is that craniofacial and ADT structures develop with regularity, allowing for predictability and determination of normal growth trajectories. Better understanding of functional morphologic relationships between skull and ADT in normal infants during this sensitive window of time may contribute to improving recognition, assessment, and treatment strategies/techniques for a number of conditions, including SIDS, cleft lip and palate, craniosynostosis, microcephaly, craniofacial syndromes among others.Support or Funding InformationGrant Funding Source: National Counsel of Technological Development – CNPq (Brazil)

When I wrote my first book African American Women Chemists I neglected to state that it was a historical book. I researched to find the first African American woman who had studied chemistry in college and worked in the field. The woman that I found was Josephine Silane Yates who studied chemistry at the Rhode Island Normal School in order to become a science teacher. She was hired by the Lincoln Institute in 1881 and later was, I believe, the first African American woman to become a professor and head a department of science. But then again there might be women who traveled out of the country to study because of racial prejudice in this country. The book ended with some women like myself who were hired as chemists in the industry before the Civil Rights Act of 1964. Therefore, I decided to write another book about the current African American women chemists who, as I say, are hiding in plain sight. To do this, I again researched women by using the web or by asking questions of people I met at American Chemical Society ACS or National Organization for the Professional Advances of Black Chemists and Chemical Engineers (NOBCChE) meetings. I asked women to tell me their life stories and allow me to take their oral history, which I recorded and which were transcribed thanks to the people at the Chemical Heritage Foundation in Philadelphia, PA. Most of the stories of these women will be archived at the CHF in their oral history collection. The women who were chosen to be in this book are an amazing group of women. Most of them are in academia because it is easy to get in touch with professors since they publish their research on the web. Some have worked for the government in the national laboratories and a few have worked in industry. Some of these women grew up in the Jim Crow south where they went to segregated schools but were lucky because they were smart and had teachers and parents who wanted them to succeed despite everything they had to go through.