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  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2766-2766
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2766-2766
    Abstract: Background: DNA methylation of gene promoters have been show to play a role in the pathogenesis of acute myeloid leukemia. We present in this study a preliminary report of the methylation status of MLH1, p16 and SOCS1 in Puertorrican patients with acute myeloid leukemia Methods: Peripheral blood was obtained from 24 patients with diagnosis of acute myeloid leukemia before their induction treatments. DNA was isolated and further modified with sodium bisulfite. Methylation-specific polymerase (MSP) chain reaction was performed to detect aberrant promoter methylation of MLH1, p16 and SOCS1. Results: A total of 24 samples were analyzed. The mean age was 49 years (range 22-71) with 17/24 patients younger than 60 years (71%). Most of the patients were female (13/24, 54%). Six patients had diploid cytogenetics (25%), 6 had low risk cytogenetics (25%) and 12 had high risk cytogenetics (50%). Fifteen patients were de Novo AML (63%). Nine patients (38%) presented with WBC counts higher than 10 × 109/L. Thirteen patients (54%) achieved a complete response at the end of the induction therapy. Methylation of MLH1 was detected in 3/24 patients (13%). Methylation of p16 was detected in 5/24 patients (21%). Methylation of SOCS1 was detected in 2/24 patients (8%). Conclusions: A tendency toward an association of methylated p16 with treatment resistance was noted. Also, methylation of SOCS1 was more common among relapsed AML patients. No correlation between methylated MLH1 gene and clinicopathological characteristics was noted. Collection of more patient's samples and correlation with clinical data and patient's ultimate outcome is ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2766. doi:10.1158/1538-7445.AM2011-2766
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 5569-5569
    Abstract: Background: DNA methylation of gene promoters have been show to play a role in the pathogenesis of acute myeloid leukemia (AML). We present in this study a preliminary report of the methylation status of MLH1, p16, SOCS1, ER and CDH1 in Puerto Rican patients with AML. Methods: Peripheral blood was obtained from 24 patients with diagnosis of acute myeloid leukemia before and after their induction treatments. DNA was isolated and further modified with sodium bisulfite. Methylation-specific polymerase (MSP) chain reaction was performed to detect aberrant promoter methylation of MLH1, p16, SOCS1, ER and CDH1. Results: Samples from a total of 24 patients were analyzed. The mean age was 47 years (range 22-70) with 21/24 patients younger than 60 years (88%). Most of the patients were female (13/24, 54%). Ten patients had diploid cytogenetics (42%), 4 had low risk cytogenetics (17%) and 10 had high risk cytogenetics (42%). Nineteen patients were de Novo AML (79%). Sixteen patients (67%) presented with WBC counts higher than 10 x 109/L. Seventeen patients (71%) achieved a complete response at the end of the induction therapy. Frequencies of gene methylation before treatment were as follows: MLH: 3/24 (13%); p16: 6/24 (25%); SOCS1:13/24 (54%); ER: 16/24 (67%) and CDH1: 4/24 (16.7%). Conclusions: No correlation between methylation status of p16 and MLH1 before treatment and clinicopathological characteristics was noted. Unmethylated CDH1 was more common among the novo AML patients. Methylation of SOCS1 was more common among patients that achieve a CR after induction therapy. This sample is a small one, so any correlation must be further tested in a more ample sample. Collection of more patient's samples and correlation with clinical data and patient's ultimate outcome is ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5569. doi:1538-7445.AM2012-5569
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 3
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 19, No. 10_Supplement ( 2010-10-01), p. A92-A92
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 19, No. 10_Supplement ( 2010-10-01), p. A92-A92
    Abstract: In acute myeloid leukemias, aberrant DNA methylation of promoter-associated CpG islands represents an important mechanism in leukemogenesis. Hypermethylation of promoters blocks transcriptional activity of genes associated with tumor suppression and cell cycle control. In this study, we evaluate the promoter methylation status of genes CDKN2A and MLH1 in a small sample of Puertorrican patients with acute myeloid leukemia. Methods: Peripheral blood was obtained from 6 patients with acute myeloid leukemia at the time of their diagnosis. Mononuclear cells were isolated by density gradient technique. DNA was isolated and further modified with sodium bisulfite. Methylation-specific polymerase (MSP) chain reaction was performed to detect the aberrant promoter methylation of CDKN2A and MLH1 genes in 6 patients with acute myeloid leukemia. Results: A total of 6 samples were analyzed. The mean age was 44 years (24-66) and most of the patients were female (5/6,83%). Four of the patients had diploid cytogenetics, one patient had t(8;21) and one had-7q cytogenetics. WBC counts at presentation were 5.35/uL (0.8-13.8). Hypermethylation of CDKN2A and MLH1 was not detected in any of the samples. Conclusions: Hypermethylation of CDKN2Aand MLH1 was not seen in the first six samples analyzed in this cohort of Puertorrican patients. Collection of more patient's samples and correlation with clinical data is ongoing. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A92.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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  • 4
    In: Blood, American Society of Hematology, Vol. 105, No. 3 ( 2005-02-01), p. 1366-1367
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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  • 5
    In: Rehabilitation Oncology, Ovid Technologies (Wolters Kluwer Health), Vol. 39, No. 4 ( 2021-10), p. 175-183
    Abstract: Home-based exercise interventions might be a desirable long-term option for breast cancer survivors to enhance compliance and long-term health benefits. Purpose: To assess the effectiveness of a home-based intervention aimed at helping survivors of breast cancer meet the physical activity guidelines of the American College of Sports Medicine. Methods: Eighty-nine women (age: 55.4 ± 10 years; body mass index: 31 ± 6.5 kg/m 2 ) from 2 cancer centers serving Hispanic women participated in this study. Women underwent a baseline assessment of cardiorespiratory fitness, muscle endurance and strength, flexibility, range of motion, and extremity disability. After baseline measures, women were randomized into a control or exercise group. The exercise intervention consisted of a walking program, elastic band strengthening, and flexibility exercises performed at home. The outcome measures were reassessed 16 weeks after baseline measures. Results: The intervention showed a strong effect of time on muscle strength and shoulder range of motion, and time and group for self-reported disability. There were no differences in sedentary behavior, physical fitness, and disability measures across intervention groups, including both exercise groups combined and changes over time between intervention groups. Conclusion: It appears that a home-based intervention affects only upper-body strength and related disability, indicating that other components might need closer monitoring for significant changes to occur across time.
    Type of Medium: Online Resource
    ISSN: 2168-3808
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 6
    In: American Journal of Gastroenterology, Ovid Technologies (Wolters Kluwer Health), Vol. 115, No. 1 ( 2020-10), p. S1133-S1133
    Type of Medium: Online Resource
    ISSN: 0002-9270 , 1572-0241
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 7
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 886-886
    Abstract: All-trans-retinoic acid (ATRA) induces growth inhibition, differentiation and apoptosis in acute promyelocytic leukemia (APL) characterized by t(15;17), which leads to expression of PML-RARa and differentiation arrest. ATRA treatment alone results in complete remission (CR) about 90% of APL patients. However these remissions are transient and APL patients commonly become resistant to ATRA therapy. Recently, arsenic trioxide, As(2)O(3), was proven to be highly effective in inducing CRs not only in relapsed after ATRA and primary APL patients. Despite the well documented clinical efficacy ATRA and As(2)O(3) in APL, precise downstream molecular mechanisms of action of these agents and the molecular mechanisms responsible for the resistance largely remain unknown. Recently, employing comprehensive proteomics methods we studied molecular mechanisms of ATRA-induced growth inhibition in APL cells. We reported that ATRA induces translational suppression through multiple posttranscriptional mechanisms involved in translation initiation and elongation phases (Harris & Ozpolat et al, Blood, 104 (5) 2004). We also demonstrated that ATRA inhibits expression translation initiation factors including IF2, eIF4AI, eIF4G, eIF5, eIF6 but upregulates expression of translation inhibitor DAP5/p97/NAT1 in APL cells. Translational control of gene expression has been identified as an important regulatory mechanism for gene products involved in regulation of cell proliferation, differentiation and apoptosis. Programmed cell death 4(PDCD4) inhibits cap-dependent translation and exerts transformation-suppressing activity by inhibiting the helicase activity of eIF4A. . Here we investigated whether PDCD4 plays a role in ATRA-induced growth inhibition and terminal differentiation by mediating translational suppression. We found for the first time that ATRA (1 mM) and As(2)O(3) ( 0.4 mM and 2 mM) induced PDCD4 expression at mRNA and protein level detected by RT-PCR and western blotting analyses, respectively, after 24 h of treatment in NB4 cells. As(2)O(3) induced maximum PDCD4 protein expression at 72 h of treatment in NB4 cells ATRA induced PDCD4 mRNA expression in ATRA responsive human acute myeloid leukemia cells (HL-60) but not in ATRA-resistant HL60 cells (HL-60R), which express a point mutation in ATRA binding domain of RARa, suggesting PDCD4 expression is mediated through retinoid receptor alpha in HL-60 leukemia cells. Overall data suggest that translational control may play a role in ATRA-induced differentiation and As(2)O(3)-induced effects. We are currently determining whether other retinoid receptors are involved in ATRA-induced expression of PDCD4 and testing the hypothesis that whether PDCD4-mediated translational suppression is critical to ATRA-induced APL cell differentiation. Activation of these pathways that lead to translational suppression reveals a novel mechanism of ATRA action and provide novel insights into ATRA-induced differentiation program in APL cells.Better understanding of posttranscriptional control of gene expression may offer targets for the differentiation therapy and chemo preventive strategies.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2017
    In:  Journal of Immigrant and Minority Health Vol. 19, No. 2 ( 2017-4), p. 341-348
    In: Journal of Immigrant and Minority Health, Springer Science and Business Media LLC, Vol. 19, No. 2 ( 2017-4), p. 341-348
    Type of Medium: Online Resource
    ISSN: 1557-1912 , 1557-1920
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
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  • 9
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 31, No. 1_Supplement ( 2022-01-01), p. PO-254-PO-254
    Abstract: Introduction: Anal cancer is increasing in the general population of Puerto Rico. Anal cytology is currently the standardized method for screening among populations at higher risk for developing anal high-grade squamous intraepithelial lesions (HSIL), the precursor lesion of anal cancer. However, studies have shown that anal cytology alone underestimates the anal lesion grade compared to the gold standard test, high-resolution anoscopy (HRA). While studies with both anal histology and cytology confirmed results are limited, the validity of cytology as a screening test seems to improve with more extensive HSILs. We evaluated the validity of anal cytology in detecting HSIL overall and by anal HSIL extension in a clinic-based Hispanic population. Methods: Data from baseline visits and examination from October 2014 to April 2021 of the Anal Neoplasia Clinic at the University of Puerto Rico Comprehensive Cancer Center were analyzed. Individuals who attended the clinic were eligible if they had completed anal cytology testing, HR-HPV typing, and HRA with biopsy. During the baseline visit basic demographic and clinical characteristics were collected. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated by comparing anal cytology results with biopsy results from HRA, overall and by extent of histologically confirmed HSIL, defined as number of octants in the anal canal affected by HSIL (1 vs 2+). Results: Among 431 patients, 67.5% were male and the mean age was 43.57 +/- 13.27 years. Overall, 75.2% were living with HIV and 76.8% tested positive for HR-HPV. Persons diagnosed with any type of squamous intraepithelial lesion (SIL) via anal cytology and histology were 71.46% and 84.22%, respectively. In contrast, while anal HSIL was detected in only 2.09% of individuals through anal cytology, it was detected in 40.37% through biopsy-confirmed histology samples. The overall sensitivity of anal cytology compared to histology was 83.9% (95% CI: 77.6%-89%), whereas the specificity was 37% (95% CI: 31%-43.2%). Among persons with biopsy-confirmed HSIL, when comparing anal cytology to histology by HSIL extension (1 vs. 2+ octants affected) the sensitivity remained similar for both groups (83.7% vs. 84.1%), while specificity was the same with 37%. While the PPV decreased with HSIL extension (32.2% vs. 29.9%) and the NPV increased (86.4% vs. 88.0%), these indicators act as poor predictors of disease status in both groups. Conclusion: In this Hispanic population, anal cytology underestimates biopsy-confirmed HSIL and its performance in detected anal HSIL did not improve with HSIL extension. While future studies with larger sample sizes are needed to further validate research findings, this study emphasizes the need to continue to optimize anal cancer screening methods in high-risk populations. Determining the best way to detect and treat cellular abnormalities will help prevent further disease progression and anal cancer development. AMC-NCI Grant #'s: UM1CA121947, 2U54CA096297-17, R25CA240120. Citation Format: Kandyce G. Keller, Jeslie M. Ramos-Cartagena, MS, Humberto M. Guiot, Cristina Munoz, Yolanda Rodriguez, Vivian Colon-Lopez, Ashish A. Deshmukh, Maribel Tirado-Gomez, Ana Patricia Ortiz. Assessment of the performance of anal cytology as a screening tool for anal high-grade squamous intraepithelial lesions by extent of disease in a clinic-based sample in Puerto Rico [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-254.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 10
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 2241-2241
    Abstract: Introduction: Anal cancer incidence has been rising rapidly in Puerto Rico. The ANCHOR study showed that treating high-grade squamous intraepithelial lesions (HSILs) significantly reduces anal cancer incidence. Limited research has been done to understand the validity and associated costs of screening tools used to detect anal lesions in Hispanic populations. We aimed to evaluate the clinical performance (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV] ) and screening test costs in the clinic-based sample. Understanding the accuracy and costs of screening tools can guide interventions in resource-limited settings to broaden the availability of effective, low-cost screening options and promote anal cancer prevention. Methods: The cross-sectionally analyzed data was collected (May 2015 - June 2021) by the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center. The clinic predominantly serves referred adults (≥18 years old). Patients were included in the analyses if they had complete results for anal cytology, high-resolution anoscopy (HRA) with biopsy, and anal high-risk HPV (HR-HPV) typing (n=436). Sensitivity, specificity, PPV, and NPV were estimated to evaluate the clinical performance of anal cytology alone and in combination with HR-HPV typing in the detection of histologically confirmed anal HSIL (Gold standard). Analyses were stratified by risk group (women, MSM, and heterosexual men) and HIV status. Evaluation of cost-effective alternative screening strategies is currently ongoing. Results: The mean age of our sample was 44 ± 13 years; more than half (67%) were male. HIV-infected MSM, HIV-infected women, and HIV-negative MSM comprised 45.4%, 22.2%, 13.3% of our sample, respectively. 40% of the sample had HSIL and 69% tested positive for HR-HPV. Measured against the gold standard, we found that co-testing (anal cytology and HR-HPV typing) increased the sensitivity in the groups evaluated and decreased specificity in some. Among HIV-infected MSM, the sensitivity of anal cytology alone to detect HSIL was 84.7%, whereas specificity was 30.0%. Although the sensitivity of the 2 tests combined (anal cytology and HR-HPV typing) to detect histologically confirmed HSIL increased (91.8%), the specificity decreased (22.0%). Overall, the sensitivity of cytology alone was higher in women compared to men and among PLWH compared to HIV-negative individuals. Conclusion: While higher sensitivity for HSIL detection was seen for cytology alone for women and HIV-infected populations, co-testing increased the sensitivity for HSILs detection. Understanding the accuracy and cost of screening tools can guide interventions to broaden the availability of effective, low-cost screening options and promote anal cancer prevention. Access and availability of these tools in a wide context of communities must be considered. Citation Format: Kandyce G. Keller, Celeste Leigh Pearce, Karen J. Ortiz-Ortiz, Jeslie M. Ramos-Cartagena, Humberto Guiot, Vivian Colón-López, Ashish A. Deshmukh, Maribel Tirado-Gómez, Ana Patricia Ortiz. Evaluating anal cancer screening approaches in high-risk populations in Puerto Rico [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 2241.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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