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1.
Quant Imaging Med Surg ; 14(7): 4362-4375, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39022288

RESUMO

Background: Uterine fibroid (UF) growth rate and future morbidity cannot be predicted. This can lead to sub-optimal clinical management, with women being lost to follow-up and later presenting with severe disease that may require hospitalization, transfusions, and urgent surgical interventions. Multi-parametric quantitative magnetic resonance imaging (MRI) could provide a biomarker to predict growth rate facilitating better-informed disease management and better clinical outcomes. We assessed the ability of putative quantitative and qualitative MRI predictive factors to predict UF growth rate. Methods: Twenty women with UFs were recruited and completed baseline and follow-up MRI exams, 1-2.5 years apart. The subjects filled out symptom severity and health-related quality of life questionnaires at each visit. A standard clinical pelvic MRI non-contrast exam was performed at each visit, followed by a contrast-enhanced multi-parametric quantitative MRI (mp-qMRI) exam with T2, T2*, and apparent diffusion coefficient (ADC) mapping and dynamic contrast-enhanced MRI. Up to 3 largest fibroids were identified and outlined on the T2-weighted sequence. Fibroid morphology and enhancement patterns were qualitatively assessed on dynamic contrast-enhanced MRI. The UFs' volumes and average T2, T2*, and ADC values were calculated. Pearson correlation coefficients were calculated between UF growth rate and T2, T2*, ADC, and baseline volume. Multiple logistic regression and receiver operating characteristic (ROC) analysis were performed to predict fast-growing UFs using combinations of up to 2 significant predictors. A significance level of alpha =0.05 was used. Results: Forty-four fibroids in 20 women had growth rate measurement available, and 36 fibroids in 16 women had follow-up quantitative MRI available. The distribution of fibroid growth rate was skewed, with approximately 20% of the fibroids exhibiting fast growth (>10 cc/year). However, there were no significant changes in median baseline and follow-up values of symptom severity and health-related quality of life scores. There was no change in average T2, T2*, and ADC at follow-up exams and there was a moderate to strong correlation to the fibroid growth rate in baseline volume and average T2 and ADC in slow-growing fibroids (<10 cc/year). A multiple logistic regression to identify fast growing UFs (>10 cc/year) achieved an area under the curve (AUC) of 0.80 with specificity of 69% at 100% sensitivity. Conclusions: The mp-qMRI parameters T2, ADC, and UF volume obtained at the time of initial fibroid diagnosis may be able to predict UF growth rate. Mp-qMRI could be integrated into the management of UFs, for individualized care and improved clinical outcomes.

2.
Radiol Artif Intell ; 5(6): e220299, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38074785

RESUMO

Purpose: To externally evaluate a mammography-based deep learning (DL) model (Mirai) in a high-risk racially diverse population and compare its performance with other mammographic measures. Materials and Methods: A total of 6435 screening mammograms in 2096 female patients (median age, 56.4 years ± 11.2 [SD]) enrolled in a hospital-based case-control study from 2006 to 2020 were retrospectively evaluated. Pathologically confirmed breast cancer was the primary outcome. Mirai scores were the primary predictors. Breast density and Breast Imaging Reporting and Data System (BI-RADS) assessment categories were comparative predictors. Performance was evaluated using area under the receiver operating characteristic curve (AUC) and concordance index analyses. Results: Mirai achieved 1- and 5-year AUCs of 0.71 (95% CI: 0.68, 0.74) and 0.65 (95% CI: 0.64, 0.67), respectively. One-year AUCs for nondense versus dense breasts were 0.72 versus 0.58 (P = .10). There was no evidence of a difference in near-term discrimination performance between BI-RADS and Mirai (1-year AUC, 0.73 vs 0.68; P = .34). For longer-term prediction (2-5 years), Mirai outperformed BI-RADS assessment (5-year AUC, 0.63 vs 0.54; P < .001). Using only images of the unaffected breast reduced the discriminatory performance of the DL model (P < .001 at all time points), suggesting that its predictions are likely dependent on the detection of ipsilateral premalignant patterns. Conclusion: A mammography DL model showed good performance in a high-risk external dataset enriched for African American patients, benign breast disease, and BRCA mutation carriers, and study findings suggest that the model performance is likely driven by the detection of precancerous changes.Keywords: Breast, Cancer, Computer Applications, Convolutional Neural Network, Deep Learning Algorithms, Informatics, Epidemiology, Machine Learning, Mammography, Oncology, Radiomics Supplemental material is available for this article. © RSNA, 2023See also commentary by Kontos and Kalpathy-Cramer in this issue.

3.
Magn Reson Imaging ; 104: 9-15, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37611646

RESUMO

PURPOSE: To assess whether measurement of the bilateral asymmetry of semiquantitative and quantitative perfusion parameters from ultrafast dynamic contrast-enhanced MRI (DCE-MRI), allows early prediction of pathologic response after neoadjuvant chemotherapy (NAC) in patients with HER2+ breast cancer. MATERIALS AND METHODS: Twenty-eight female patients with HER2+ breast cancer treated with NAC who underwent pre-NAC ultrafast DCE-MRI (3-9 s/phase) were enrolled for this study. Four semiquantitative and two quantitative parenchymal parameters were calculated for each patient. Ipsilateral/contralateral (I/C) ratio (for four parameters) and the difference between (for two parameters) ipsi- and contra-lateral parenchymal kinetic parameters (kBPE) were compared for patients with pathologic complete response (pCR) and those having residual disease. Lasso regression with leave-one-out cross validation was used to determine the optimal combination of parameters for a regression model and multivariable logistic regression was used to identify independent predictors for pCR. Chi-squared test, two-sided t-test and Kruskal-Wallis test were used. RESULTS: The Ktrans I/C ratio cutoff value of 1.11 had a sensitivity of 83.3% and specificity of 75% for pCR. The ve I/C ratio cutoff value of 1.1 had a sensitivity of 75% and specificity of 81.3% for pCR. The area under the receiver operating characteristic curve of the three-kBPE parameter model, including initial area under the enhancement curve (AUC30) I/C ratio, KtransI/C ratio and ve I/C ratio, was 0.89 with sensitivity of 91.7% at specificity of 81.3%. CONCLUSION: Quantitative assessment of bilateral asymmetry kBPE from pre-NAC ultrafast DCE-MRI can predict pCR in patients with HER2+ breast cancer.

4.
J Breast Imaging ; 5(2): 203-208, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38416929

RESUMO

Creating a comprehensive didactic curriculum for breast imaging fellows can be a demanding undertaking, especially considering that most breast practices are understaffed because of the COVID-19 pandemic and amid rising clinical volumes. This leaves little time for didactic education. In this article, we present our approach to creating a collaborative weekly multidisciplinary didactic lecture series involving multiple institutions, using the Society of Breast Imaging's suggested fellowship curriculum as the foundation. We discuss the advantages for both trainees and faculty, including fostering camaraderie, networking, and engagement among breast imaging fellows. Faculty have the opportunity for professional development by leveraging their clinical expertise through selecting didactic topics in their niche. This creates a pathway for speaking faculty to be recognized as regional and national experts.


Assuntos
Bolsas de Estudo , Pandemias , Humanos , Currículo , Escolaridade , Estudos Interdisciplinares
5.
Ann Surg Oncol ; 28(10): 5513-5524, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34333705

RESUMO

BACKGROUND: Two-dimensional (2D) specimen radiography (SR) and tomosynthesis (DBT) for breast cancer yield data that lack high-depth resolution. A volumetric specimen imager (VSI) was developed to provide full-3D and thin-slice cross-sectional visualization at a 360° view angle. The purpose of this prospective trial was to compare VSI, 2D SR, and DBT interpretation of lumpectomy margin status with the final pathologic margin status of breast lumpectomy specimens. METHODS: The study enrolled 200 cases from two institutions. After standard imaging and interpretation was performed, the main lumpectomy specimen was imaged with the VSI device. Image interpretation was performed by three radiologists after surgery based on VSI, 2D SR, and DBT. A receiver operating characteristic (ROC) curve was created for each method. The area under the curve (AUC) was computed to characterize the performance of the imaging method interpreted by each user. RESULTS: From 200 lesions, 1200 margins were interpreted. The AUC values of VSI for the three radiologists were respectively 0.91, 0.90, and 0.94, showing relative improvement over the AUCs of 2D SR by 54%, 13%, and 40% and DBT by 32% and 11%, respectively. The VSI has sensitivity ranging from 91 to 94%, specificity ranging from 81 to 85%, a positive predictive value ranging from 25 to 30%, and a negative predicative value of 99%. CONCLUSIONS: The ROC curves of the VSI were higher than those of the other specimen imaging methods. Full-3D specimen imaging can improve the correlation between the main lumpectomy specimen margin status and surgical pathology. The findings from this study suggest that using the VSI device for intraoperative margin assessment could further reduce the re-excision rates for women with malignant disease.


Assuntos
Neoplasias da Mama , Mastectomia Segmentar , Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Estudos Transversais , Feminino , Humanos , Mamografia , Estudos Prospectivos
6.
J Biosci ; 452020.
Artigo em Inglês | MEDLINE | ID: mdl-32975231

RESUMO

In this study we have investigated the effects of a tumour suppressor microRNA, miR-214, on gene expression in HPV-positive (CaSki) and HPV-negative cervical cancer cells (C33A) by RNA sequencing using next generation sequencing. The HPV-positive and HPV-negative cervical cancer cells were either miR-214- knocked-out or miR-214-overexpressed. Gene expression analysis showed that a total of 904 genes were upregulated and 365 genes were downregulated between HPV-positive and HPV-negative cervical cancer cells with a fold change of +/- 2. Furthermore, 11 differentially expressed and relevant genes (TNFAIP3, RAB25, MET, CYP1B1, NDRG1, CD24, LOXL2, CD44, PMS2, LATS1 and MDM1) which showed a fold change of +/-5 were selected to confirm by real-time PCR. This study represents the first report of miR-214 on global gene expression in the context of HPV.


Assuntos
MicroRNAs/genética , Proteínas de Neoplasias/genética , Infecções por Papillomavirus/genética , Transcriptoma , Neoplasias do Colo do Útero/genética , Aminoácido Oxirredutases/genética , Aminoácido Oxirredutases/metabolismo , Antígeno CD24/genética , Antígeno CD24/metabolismo , Sistemas CRISPR-Cas , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP1B1/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Endonuclease PMS2 de Reparo de Erro de Pareamento/metabolismo , Proteínas de Neoplasias/metabolismo , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo
7.
Genomics ; 112(2): 1490-1499, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31465786

RESUMO

In this study, we investigate the effect of one such micro RNA, miR-214 which is frequently down-regulated in cervical cancer. In this study, we either CRISPR knocked out or overexpressed miR-214 in cervical cancer cells and analyzed the global mRNA expression by Next Generation Sequencing (NGS) It was observed that a total of 108 genes were upregulated and 178 downregulated between the samples, above and below the baseline respectively. Gene Ontology and KEGG pathway analysis reveal distinct biological processes and pathways. Analysis of gene regulatory networks also gave different network patterns in the two samples. We confirmed the RNA sequencing data for 10 genes; IFIF27, SMAD3, COX11, TP53INP1, ABL2, FGF8, TNFAIP3, NRG1, SP3 and MDM4 by Real-time PCR. This is the first report on the effect of miR-214 on global mRNA profile in cervical cancer cells. This study also reports new biomarkers for cervical cancer prognosis.


Assuntos
Biomarcadores Tumorais/genética , MicroRNAs/genética , Transcriptoma , Neoplasias do Colo do Útero/genética , Biomarcadores Tumorais/metabolismo , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , MicroRNAs/metabolismo
8.
J Am Coll Radiol ; 17(2): 238-247, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31628897

RESUMO

OBJECTIVE: To evaluate the impact of comorbid conditions and age on mammography use. METHODS: We used data from the 2011 to 2015 Medical Expenditure Panel Survey, which contained records for 40,752 women over the age of 40. Use was defined as a mammogram within the previous 1 or 2 years, analyzed separately. A logit model was employed to evaluate associations between use and comorbidities and age. Statistical significance was defined by a P < .05 by two-sided test. RESULTS: Of the 36,575 women in our study sample, 45.9%, 43.6%, 3.9%, and 5.7% reported a history of hypertension (HTN), hyperlipidemia (HLD), prior heart attack (MI), and prior stroke, respectively. Among women without a comorbid condition, there was 47.3% annual mammography use. HTN and HLD were associated with increased use (2.5 and 6.8 percentage points [pp], P< .01). In comparison, prior MI was associated with decreased annual use (-8.2 pp, P < .01). Prior stroke was not significantly associated with annual mammography (-1.5 pp, P = .42). Results were similar for biennial use. The age trend in use showed that the age with maximum screening use was approximately 60 years. DISCUSSION: Mammography use was higher in patients with HTN and HLD and lower in patients with prior MI and stroke, which may reflect differences in comorbidity-related general health care use. Use increased until it peaked around age 60. An understanding of how mammography use naturally evolves as people age may help better target specific populations and improve overall use of preventive care.


Assuntos
Neoplasias da Mama , Mamografia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Comorbidade , Feminino , Humanos , Modelos Logísticos , Programas de Rastreamento , Pessoa de Meia-Idade , Fatores de Tempo
9.
J Med Imaging (Bellingham) ; 6(3): 034502, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31592438

RESUMO

The purpose of this study was to evaluate breast MRI radiomics in predicting, prior to any treatment, the response to neoadjuvant chemotherapy (NAC) in patients with invasive lymph node (LN)-positive breast cancer for two tasks: (1) prediction of pathologic complete response and (2) prediction of post-NAC LN status. Our study included 158 patients, with 19 showing post-NAC complete pathologic response (pathologic TNM stage T0,N0,MX) and 139 showing incomplete response. Forty-two patients were post-NAC LN-negative, and 116 were post-NAC LN-positive. We further analyzed prediction of response by hormone receptor subtype of the primary cancer (77 hormone receptor-positive, 39 HER2-enriched, 38 triple negative, and 4 cancers with unknown receptor status). Only pre-NAC MRIs underwent computer analysis, initialized by an expert breast radiologist indicating index cancers and metastatic axillary sentinel LNs on DCE-MRI images. Forty-nine computer-extracted radiomics features were obtained, both for the primary cancers and for the metastatic sentinel LNs. Since the dataset contained MRIs acquired at 1.5 T and at 3.0 T, we eliminated features affected by magnet strength using the Mann-Whitney U-test with the null-hypothesis that 1.5 T and 3.0 T samples were selected from populations having the same distribution. Bootstrapping and ROC analysis were used to assess performance of individual features in the two classification tasks. Eighteen features appeared unaffected by magnet strength. Pre-NAC tumor features generally appeared uninformative in predicting response to therapy. In contrast, some pre-NAC LN features were able to predict response: two pre-NAC LN features were able to predict pathologic complete response (area under the ROC curve (AUC) up to 0.82 [0.70; 0.88]), and another two were able to predict post-NAC LN-status (AUC up to 0.72 [0.62; 0.77]), respectively. In the analysis by a hormone receptor subtype, several potentially useful features were identified for predicting response to therapy in the hormone receptor-positive and HER2-enriched cancers.

10.
Sci Rep ; 9(1): 1631, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30733556

RESUMO

Estimation of phytoene, lycopene, ß-carotene, lutein, and zeaxanthin in grains of white, brown and purple cultivars of rice revealed marked differences in the levels of these carotenoid intermediates amongst the cultivars. Grains of white rice did not show any significant accumulation of carotenoid intermediates at any stage of development. On the other hand, grains of the purple cultivar accumulated 49.16 ± 5 µg of ß-carotene, 28.89 ± 3.2 µg of lutein and 34.65 ± 4.6 µg of zeaxanthin per gm of grain fresh weight. In addition to PSY1, higher expression of ßLCY than εLCY appears to be an important factor in determining the flux of pathway towards synthesis of ß-ß branch carotenoids in purple rice. This cultivar showed a higher fold change in carotenoid precursors during transition from milky to doughing stages and an enhanced flux of lycopene towards ß-carotene during grain maturation. Our results indicate that higher level of carotenoids in purple rice is a consequence of higher expression of genes involved in pyruvate metabolism as well as those involved in carotenoid biosynthesis such as PSY1, PDS and ß-LCY. Co-expression networking revealed a strong positive relationship between the expression profiles of genes involved in carotenoid biosynthesis and genes coding for geranylgeranyl transferase type II, glutathione S-transferase, DnaJ and SET domain containing proteins as well as MADS26 and R2R3MYB family of transcription factors.


Assuntos
Carotenoides/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Oryza/crescimento & desenvolvimento , Pigmentação/genética , Proteínas de Plantas/metabolismo , Ácido Pirúvico/metabolismo , Reprodutibilidade dos Testes , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo
11.
Clin Cancer Res ; 25(6): 1786-1794, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30154229

RESUMO

PURPOSE: To establish a cohort of high-risk women undergoing intensive surveillance for breast cancer.Experimental Design: We performed dynamic contrast-enhanced MRI every 6 months in conjunction with annual mammography (MG). Eligible participants had a cumulative lifetime breast cancer risk ≥20% and/or tested positive for a pathogenic mutation in a known breast cancer susceptibility gene. RESULTS: Between 2004 and 2016, we prospectively enrolled 295 women, including 157 mutation carriers (75 BRCA1, 61 BRCA2); participants' mean age at entry was 43.3 years. Seventeen cancers were later diagnosed: 4 ductal carcinoma in situ (DCIS) and 13 early-stage invasive breast cancers. Fifteen cancers occurred in mutation carriers (11 BRCA1, 3 BRCA2, 1 CDH1). Median size of the invasive cancers was 0.61 cm. No patients had lymph node metastasis at time of diagnosis, and no interval invasive cancers occurred. The sensitivity of biannual MRI alone was 88.2% and annual MG plus biannual MRI was 94.1%. The cancer detection rate of biannual MRI alone was 0.7% per 100 screening episodes, which is similar to the cancer detection rate of 0.7% per 100 screening episodes for annual MG plus biannual MRI. The number of recalls and biopsies needed to detect one cancer by biannual MRI were 2.8 and 1.7 in BRCA1 carriers, 12.0 and 8.0 in BRCA2 carriers, and 11.7 and 5.0 in non-BRCA1/2 carriers, respectively. CONCLUSIONS: Biannual MRI performed well for early detection of invasive breast cancer in genomically stratified high-risk women. No benefit was associated with annual MG screening plus biannual MRI screening.See related commentary by Kuhl and Schrading, p. 1693.


Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer/métodos , Imageamento por Ressonância Magnética/métodos , Programas de Rastreamento/métodos , Adulto , Biópsia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Predisposição Genética para Doença , Humanos , Mamografia , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Estudos Prospectivos
12.
Clin Imaging ; 48: 69-73, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29035756

RESUMO

PURPOSE: To evaluate whether the disease status of the pre-neoadjuvant chemotherapy (NAC) core biopsied lymph node (preNACBxLN) in patients with node positive breast cancer corresponds to nodal status of all surgically retrieved lymph nodes (LNs) post-NAC and whether wire localization of this LN is feasible. MATERIALS AND METHODS: HIPPA compliant IRB approved retrospective study including breast cancer patients (a.) with preNACBxLN confirmed metastases, (b.) who received NAC, and (c.) underwent wire localization of the preNACBxLN. Electronic medical records were reviewed. Fisher's exact test was used to compare differences in residual disease post-NAC among breast cancer subtypes. RESULTS: 28 women with node positive breast cancer underwent ultrasound guided wire localization of the preNACBxLN, without complication. There was no evidence of residual nodal disease for 16 patients, with mean 4.4 (median 4) LNs resected. 12 patients had residual nodal metastases, with mean 9.2 (median 7) LNs resected and mean 2.3 (median 2) LNs with tumor involvement. 11 patients had metastases detected within the localized LN. One patient had micrometastasis in a sentinel LN, despite no residual disease in the preNACBxLN. Patients with luminal A/B breast cancer more often had residual nodal metastases (86%) at pathology, as compared to patients with HER2+ (20%) and Triple Negative breast cancer (50%), though not quite achieving statistical significance (p=0.055). CONCLUSION: Ultrasound guided wire localization of the preNACBxLN is feasible and may improve detection of residual tumor in patients post-NAC.


Assuntos
Neoplasias da Mama/patologia , Linfonodos/patologia , Biópsia de Linfonodo Sentinela/métodos , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila/patologia , Neoplasias da Mama/tratamento farmacológico , Estudos de Viabilidade , Feminino , Humanos , Metástase Linfática/diagnóstico , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Retrospectivos
13.
Mol Ther Nucleic Acids ; 9: 349-364, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29246314

RESUMO

Inhibition of the interaction between p53 and HDM2 is an effective therapeutic strategy in cancers that harbor a wild-type p53 protein such as retinoblastoma (RB). Nanoparticle-based delivery of therapeutic molecules has been shown to be advantageous in localized delivery, including to the eye, by overcoming ocular barriers. In this study, we utilized biocompatible gold nanoparticles (GNPs) to deliver anti-HDM2 peptide to RB cells. Characterization studies suggested that GNP-HDM2 was stable in biologically relevant solvents and had optimal cellular internalization capability, the primary requirement of any therapeutic molecule. GNP-HDM2 treatment in RB cells in vitro suggested that they function by arresting RB cells at the G2M phase of the cell cycle and initiating apoptosis. Analysis of molecular changes in GNP-HDM2-treated cells by qRT-PCR and western blotting revealed that the p53 protein was upregulated; however, transactivation of its downstream targets was minimal, except for the PUMA-BCl2 and Bax axis. Global gene expression and in silico bioinformatic analysis of GNP-HDM2-treated cells suggested that upregulation of p53 might presumptively mediate apoptosis through the induction of p53-inducible miRNAs.

14.
Clin Imaging ; 45: 96-104, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28645096

RESUMO

Incidental focal FDG uptake in the breast or axilla on PET/CT performed for evaluation of extra-mammary primary disease presents a diagnostic challenge. Radiologists must consider a broad differential diagnosis, assess clinical history, and judiciously employ other imaging modalities such as mammography, ultrasound and MRI in the pursuit of findings which help narrow the differential diagnosis. Tissue sampling may be reserved for nondiagnostic imaging scenarios.


Assuntos
Axila/diagnóstico por imagem , Doenças Mamárias/diagnóstico , Mama/diagnóstico por imagem , Fluordesoxiglucose F18/farmacologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Diagnóstico Diferencial , Feminino , Humanos , Compostos Radiofarmacêuticos/farmacologia
15.
Genom Data ; 3: 8-14, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26484141

RESUMO

The role of Mithramycin as an anticancer drug has been well studied. Sarcoma is a type of cancer arising from cells of mesenchymal origin. Though incidence of sarcoma is not of significant percentage, it becomes vital to understand the role of Mithramycin in controlling tumor progression of sarcoma. In this article, we have analyzed the global gene expression profile changes induced by Mithramycin in two different sarcoma lines from whole genome gene expression profiling microarray data. We have found that the primary mode of action of Mithramycin is by global repression of key cellular processes and gene families like phosphoproteins, kinases, alternative splicing, regulation of transcription, DNA binding, regulation of histone acetylation, negative regulation of gene expression, chromosome organization or chromatin assembly and cytoskeleton.

16.
FEBS Open Bio ; 4: 987-95, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25473595

RESUMO

Mithramycin (MTR) is a clinically approved DNA-binding antitumor antibiotic currently in Phase 2 clinical trials at National Institutes of Health for treatment of osteosarcoma. In view of the resurgence in the studies of this generic antibiotic as a human medicine, we have examined the binding properties of MTR with the integral component of chromatin - histone proteins - as a part of our broad objective to classify DNA-binding molecules in terms of their ability to bind chromosomal DNA alone (single binding mode) or both histones and chromosomal DNA (dual binding mode). The present report shows that besides DNA, MTR also binds to core histones present in chromatin and thus possesses the property of dual binding in the chromatin context. In contrast to the MTR-DNA interaction, association of MTR with histones does not require obligatory presence of bivalent metal ion like Mg(2+). As a consequence of its ability to interact with core histones, MTR inhibits histone H3 acetylation at lysine 18, an important signature of active chromatin, in vitro and ex vivo. Reanalysis of microarray data of Ewing sarcoma cell lines shows that upon MTR treatment there is a significant down regulation of genes, possibly implicating a repression of H3K18Ac-enriched genes apart from DNA-binding transcription factors. Association of MTR with core histones and its ability to alter post-translational modification of histone H3 clearly indicates an additional mode of action of this anticancer drug that could be implicated in novel therapeutic strategies.

17.
AJR Am J Roentgenol ; 202(2): 289-92, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24450667

RESUMO

OBJECTIVE: The purposes of this study were to assess the importance of a personal history of breast cancer as a risk factor for patients referred for screening breast MRI and to evaluate the importance of this risk factor compared with family history. MATERIALS AND METHODS: A retrospective review of screening breast MRI performed from 2004 to 2012 included a total of 702 patients, 465 of whom had undergone annual MRI and 237 of whom had undergone MRI every 6 months as part of a research protocol. RESULTS: Of the patients screened, 208 had a personal history of breast cancer, and 345 had a family history as the sole risk factor. An additional 97 patients had both risk factors. The absolute risk for detection of breast cancer at screening MRI among patients with a personal history of cancer was 2.8% (95% CI, 0.6-5.2%). The absolute risk for patients with a strong family history of cancer was 2.0% (95% CI, 0.5-3.5%). The relative risk for detection of breast cancer given a personal history was 1.42 (95% CI, 0.48-4.17) compared with family history. The relative risk when both risk factors were present compared with having only a family history was 3.04 (95% CI, 1.05-8.86). CONCLUSION: A personal history of breast cancer is an important risk factor for the development of subsequent breast cancer. Given the results, consideration should be given to MRI screening of patients with a personal history of breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico , Imageamento por Ressonância Magnética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Programas de Rastreamento , Meglumina/análogos & derivados , Pessoa de Meia-Idade , Compostos Organometálicos , Estudos Retrospectivos , Fatores de Risco
18.
Acad Radiol ; 20(11): 1399-404, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24119352

RESUMO

PURPOSE: To compare magnetic resonance imaging (MRI) and ultrasound (US) for axillary lymph node (LN) staging in breast cancer patients in an observer-performance study. MATERIALS AND METHODS: An observer-performance study was conducted with five breast radiologists reviewing 50 consecutive patients of newly diagnosed invasive breast cancer with the use of ipsilateral axillary MRI and US. LN status was pathologically proved in all patients. Each observer reviewed the images in two separate sessions: one for MRI and the other for US. Observers were asked to indicate their confidence of the presence of at least one ipsilateral metastatic LN on a quasi-continuous rating scale and whether they recommend percutaneous biopsy preoperatively. Receiver operating characteristic (ROC) analysis and area under the ROC curve were used to characterize diagnostic performance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated from whether observers recommended biopsy. RESULTS: There were no statistically significant differences in each observer's performance between MRI and US, or in the performance of all observers as a group, in terms of ROC analysis. There were no statistically significant differences in sensitivity, specificity, PPV, or NPV between MRI and US, but there were statistically significant improvements in specificity and PPV from either MRI or US alone to MRI and US combined. CONCLUSIONS: Observer performance on MRI and US are comparable for axillary LN staging. When US and MRI are concordant for positive findings, higher specificity and PPV can be obtained.


Assuntos
Axila/patologia , Neoplasias da Mama/patologia , Metástase Linfática/patologia , Imageamento por Ressonância Magnética/métodos , Ultrassonografia Mamária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Sensibilidade e Especificidade
19.
Acad Radiol ; 18(12): 1467-74, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21962476

RESUMO

RATIONALE AND OBJECTIVES: The aims of this study were to evaluate high spectral and spatial resolution (HiSS) magnetic resonance imaging (MRI) for the diagnosis of breast cancer without the injection of contrast media by comparing the performance of precontrast HiSS images to that of conventional contrast-enhanced, fat-suppressed, T1-weighted images on the basis of image quality and in the task of classifying benign and malignant breast lesions. MATERIALS AND METHODS: Ten benign and 44 malignant lesions were imaged at 1.5 T with HiSS (precontrast administration) and conventional fat-suppressed imaging (3-10 minutes after contrast administration). This set of 108 images, after randomization, was evaluated by three experienced radiologists blinded to the imaging technique. Breast Imaging Reporting and Data System morphologic criteria (lesion shape, lesion margin, and internal signal intensity pattern) and final assessment were used to measure reader performance. Image quality was evaluated on the basis of boundary delineation and quality of fat suppression. An overall probability of malignancy was assigned to each lesion for HiSS and conventional images separately. RESULTS: On boundary delineation and quality of fat suppression, precontrast HiSS scored similarly to conventional postcontrast MRI. On benign versus malignant lesion separation, there was no statistically significant difference in receiver-operating characteristic performance between HiSS and conventional MRI, and HiSS met a reasonable noninferiority condition. CONCLUSIONS: Precontrast HiSS imaging is a promising approach for showing lesion morphology without blooming and other artifacts caused by contrast agents. HiSS images could be used to guide subsequent dynamic contrast-enhanced MRI scans to maximize spatial and temporal resolution in suspicious regions. HiSS MRI without contrast agent injection may be particularly important for patients at risk for contrast-induced nephrogenic systemic fibrosis or allergic reactions.


Assuntos
Neoplasias da Mama/diagnóstico , Imageamento por Ressonância Magnética/métodos , Idoso , Doenças Mamárias/diagnóstico , Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste , Gorduras , Feminino , Humanos , Aumento da Imagem , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia
20.
Indian J Pharmacol ; 42(3): 168-73, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20871769

RESUMO

OBJECTIVE: Cognitive disorders such as amnesia, attention deficit and Alzheimer's disease are emerging nightmares in the field of medicine because no exact cure exists for them, as existing nootropic agents (piractam, tacrine, metrifonate) have several limitations. The present study was undertaken to investigate the effect of Prunus amygdalus (PA) nuts on cognitive functions, total cholesterol levels and cholinesterase (ChE) activity in scopolamine-induced amnesia in rats. MATERIALS AND METHODS: The paste of PA nuts was administered orally at three doses (150, 300 and 600 mg/kg) for 7 and 14 consecutive days to the respective groups of rats. Piracetam (200 mg/kg) was used as a standard nootropic agent. Learning and memory parameters were evaluated using elevated plus maze (EPM), passive avoidance and motor activity paradigms. Brain ChE activity and serum biochemical parameters like total cholesterol, total triglycerides and glucose were evaluated. RESULTS: It was observed that PA at the above-mentioned doses after 7 and 14 days of administration in the respective groups significantly reversed scopolamine (1 mg/kg i.p.)-induced amnesia, as evidenced by a decrease in the transfer latency in the EPM task and step-down latency in the passive avoidance task. PA reduced the brain ChE activity in rats. PA also exhibited a remarkable cholesterol and triglyceride lowering property and slight increase in glucose levels in the present study. CONCLUSION: Because diminished cholinergic transmission and increase in cholesterol levels appear to be responsible for the development of amyloid plaques and dementia in Alzheimer patients, PA may prove to be a useful memory-restorative agent. It would be worthwhile to explore the potential of this plant in the management of Alzheimer's disease.

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