49 results on '"Grau AM"'
Search Results
2. Atlantic cod Gadus morhua in the Mediterranean: a surprising immigrant
- Author
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Morey, G, primary, Morales-Nin, B, additional, Riera, F, additional, Grau, A, additional, Geffen, AJ, additional, Pérez-Mayol, S, additional, Chang, MY, additional, and Grau, AM, additional
- Published
- 2012
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3. Do pingers reduce interactions between bottlenose dolphins and nets around the Balearic Islands?
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Brotons, JM, primary, Munilla, Z, additional, Grau, AM, additional, and Rendell, L, additional
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- 2008
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4. Variations in a shallow rocky reef fish community at different spatial scales in the western Mediterranean Sea
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Ordines, F, primary, Moranta, J, additional, Palmer, M, additional, Lerycke, A, additional, Suau, A, additional, Morales-Nin, B, additional, and Grau, AM, additional
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- 2005
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5. Molecular genetics of pancreatic cancer
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Bold, RJ, primary, Evans, DB, additional, Hess, KR, additional, Grau, AM, additional, Sinicrope, F, additional, Cleary, KR, additional, Chiao, PJ, additional, and Abbruzzese, JL, additional
- Published
- 1998
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6. Short preoperative treatment with erlotinib inhibits tumor cell proliferation in hormone receptor-positive breast cancers.
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Guix M, Granja Nde M, Meszoely I, Adkins TB, Wieman BM, Frierson KE, Sanchez V, Sanders ME, Grau AM, Mayer IA, Pestano G, Shyr Y, Muthuswamy S, Calvo B, Krontiras H, Krop IE, Kelley MC, and Arteaga CL
- Published
- 2008
7. Physical function disparities and breast cancer: preliminary results.
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Flores AM, Dwyer KD, Grau AM, Kelley M, Murphy BA, and Hagy BS
- Published
- 2006
8. Disease recurrence in patients undergoing mastectomy for ductal carcinoma in situ.
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Kuo MC, Sims J, Solis OK, Meszoely IM, Sweeting RS, Grau AM, Hewitt KC, Kauffmann RM, Kelley MC, and McCaffrey RL
- Abstract
Purpose: With DCIS incidence on the rise, up to 30% of patients undergo mastectomy for Ductal carcinoma in situ (DCIS) (Nash and Hwang, in: Ann Surg Oncol 30(6):3206-3214, 2023). Local recurrence rates after mastectomy for DCIS are reportedly low, but risk factors for recurrence are not known (Kim et al., in: J Cancer Res Ther 16(6):1197-1202, 2020). We aim to define risk factors associated with ipsilateral breast cancer recurrence in patients undergoing mastectomy for DCIS., Methods: We aimed to identify risk factors that may contribute to recurrence of breast cancer following mastectomy for pure DCIS. We hypothesized that close or positive mastectomy margins, age at diagnosis, extent of breast disease and mutation carriers would be associated with increased risk of recurrence. We performed a retrospective chart review of patients who underwent unilateral or bilateral mastectomies for pure DCIS at a single academic tertiary referral center from 2013 to 2023., Results: There were 165 patients who met inclusion criteria with an average length of follow-up of 39.9 months. On final surgical pathology, the average span of DCIS was 33.7 mm (± 24.6 mm). Hormone receptor positive disease was identified in 80.6% of the patient cohort. For margin status, 23 patients (14%) had < 1 mm margins on final pathology and of those, 1 received adjuvant radiation therapy and 4 returned to the OR for re-excision. Only 1 (0.6%) patient had ipsilateral disease recurrence during the study period., Conclusion: Recurrence after mastectomy for pure DCIS is a rare event and in our study sample, only one recurrence occurred. Risk factors for recurrence appear unrelated to margin status, age, extent of DCIS, or pathogenic mutation (ElSherif et al., in Am J Surg 226(5):646-651, 2023)., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
- Published
- 2024
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9. Superparamagnetic iron oxide (SPIO) for axillary mapping in patients with ductal carcinoma in situ undergoing mastectomy: single-institution experience.
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Addae JK, Sweeting RS, Meszoely IM, McCaffrey RL, Kauffmann RM, Kelley MC, Grau AM, and Hewitt K
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- Humans, Female, Male, Adolescent, Mastectomy, Retrospective Studies, Cross-Sectional Studies, Sentinel Lymph Node Biopsy methods, Axilla surgery, Axilla pathology, Magnetic Iron Oxide Nanoparticles, Lymph Nodes pathology, Carcinoma, Intraductal, Noninfiltrating diagnosis, Carcinoma, Intraductal, Noninfiltrating surgery, Carcinoma, Intraductal, Noninfiltrating pathology, Breast Neoplasms diagnosis, Breast Neoplasms surgery, Breast Neoplasms pathology, Ferric Compounds
- Abstract
Purpose: Unnecessary axillary surgery can potentially be avoided in patients with DCIS undergoing mastectomy. Current guidelines recommend upfront sentinel lymph node biopsy during the index operation due to the potential of upstaging to invasive cancer. This study reviews a single institution's experience with de-escalating axillary surgery using superparamagnetic iron oxide dye for axillary mapping in patients undergoing mastectomy for DCIS., Methods: This is a retrospective single-institution cross-sectional study. All medical records of patients who underwent mastectomy for a diagnosis of DCIS from August 2021 to January 2023 were reviewed and patients who had SPIO injected at the time of the index mastectomy were included in the study. Descriptive statistics of demographics, clinical information, pathology results, and interval sentinel lymph node biopsy were performed., Results: A total of 41 participants underwent 45 mastectomies for DCIS. The median age of the participants was 58 years (IQR = 17; range 25 to 76 years), and the majority of participants were female (97.8%). The most common indication for mastectomy was diffuse extent of disease (31.7%). On final pathology, 75.6% (34/45) of mastectomy specimens had DCIS without any type of invasion and 15.6% (7/45) had invasive cancer. Of the 7 cases with upgrade to invasive disease, 2 (28.6%) of them underwent interval sentinel lymph node biopsy. All sentinel lymph nodes biopsied were negative for cancer., Conclusion: The use of superparamagnetic iron oxide dye can prevent unnecessary axillary surgery in patients with DCIS undergoing mastectomy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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10. The Nursehound Scyliorhinus stellaris Mitochondrial Genome-Phylogeny, Relationships among Scyliorhinidae and Variability in Waters of the Balearic Islands.
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Catanese G, Morey G, Verger F, and Grau AM
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- Animals, DNA, Mitochondrial genetics, Phylogeny, RNA, Transfer genetics, Spain, Elasmobranchii genetics, Genome, Mitochondrial
- Abstract
The complete mitochondrial DNA sequence of the Nursehound Scyliorhinus stellaris has been determined for the first time and compared with congeneric species. The mitogenome sequence was 16,684 bp in length. The mitogenome is composed of 13 PCGs, 2 rRNAs, 22 transfer RNA genes and non-coding regions. The gene order of the newly sequenced mitogenome is analogous to the organization described in other vertebrate genomes. The typical conservative blocks in the control region were indicated. The phylogenetic analysis revealed a monophyletic origin of the Scyliorhininae subfamily, and within it, two subclades were identified. A significant divergence of Scyliorhinus spp. together with Poroderna patherinum in relation to the group of Cephaloscyllium spp. was observed, except for Scyliorhinus torazame , more related to this last cited clade. A hypothesis of a divergent evolution consequent to a selective pressure in different geographic areas, which lead to a global latitudinal diversity gradient, has been suggested to explain this phylogenetic reconstruction. However, convergent evolution on mitochondrial genes could also involve different species in some areas of the world.
- Published
- 2022
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11. Isotopic fractionation from deep roots to tall shoots: A forensic analysis of xylem water isotope composition in mature tropical savanna trees.
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Vega-Grau AM, McDonnell J, Schmidt S, Annandale M, and Herbohn J
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- Bayes Theorem, Isotopes, Water, Grassland, Xylem
- Abstract
Studies of plant water sources generally assume that xylem water integrates the isotopic composition (δ
2 H and δ18 O) of water sources and does not fractionate during uptake or transport along the transpiration pathway. However, woody xerophytes, halophytes, and trees in mesic environments can show isotopic fractionation from source waters. Isotopic fractionation and variation in isotope composition can affect the interpretation of tree water sources, but most studies to date have been greenhouse experiments. Here we present a field-based forensic analysis of xylem water isotope composition for 12 Eucalyptus tetrodonta and Corymbia nesophila trees. We used a 25-tonne excavator to access materials from the trees' maximum rooting depth of 3 m to their highest canopies at 38 m. Substantial within-tree variation occurred in δ2 H (-91.1‰ to -35.7‰ E. tetrodonta; -88.8‰ to -24.5‰ C. nesophila) and δ18 O (-12.3‰ to -5.0‰ E. tetrodonta; -10.9‰ to -0.3‰ C. nesophila), with different root-to-branch isotope patterns in each species. Soil water δ2 H and δ18 O dual isotope slopes (7.26 E. tetrodonta, 6.66 C. nesophila) were closest to the Local Meteoric Water Line (8.4). The dual isotope slopes of the trees decreased progressively from roots (6.45 E. tetrodonta, 6.07 C. nesophila), to stems (4.61 E. tetrodonta, 5.97 C. nesophila) and branches (4.68 E. tetrodonta, 5.67 C. nesophila), indicative of fractionation along the xylem stream. Roots of both species were more enriched in2 H and18 O than soil water at all sampled depths. Bayesian mixing model analysis showed that estimated proportions of water sourced from different depths reflected the contrasting root systems of these species. Our study adds evidence of isotopic fractionation from water uptake and along the transpiration stream in mature trees in monsoonal environments, affecting the interpretation of water sources. We discuss the findings with view of interpreting aboveground xylem water isotopic composition, incorporating knowledge of root systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
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12. Assessing relative post-release mortality for the transparent goby fishery: Environmental drivers and the utility of vitality metrics.
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Gil MDM, Palmer M, Morey G, Manjabacas A, Pastor E, Díaz-Gil C, and Grau AM
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- Animals, Geography, Models, Theoretical, Probability, Spain, Species Specificity, Surveys and Questionnaires, Survival Analysis, Time Factors, Video Recording, Environment, Fisheries, Perciformes growth & development
- Abstract
The target species (Aphia minuta and Pseudaphya ferreri) of the transparent goby fishery on Mallorca Island (Balearic Islands, western Mediterranean) are currently discarded when the maximum daily catch is exceeded or when the sorting process is unworkable. The mortality suffered by this discarded fraction remains unknown, although it may be important for resource management. Accordingly, the aims of this study were to (1) assess the environmental drivers of the relative post-release survival of the discarded target species and (2) test the correlations between post-release survival and two behavior-related variables (swimming speed and its increase after a stimulus, assessed via video recording). To do so, mortality of the target species from 47 hauls sampled under normal fishing boat operations was monitored when the gear was onboard and after a few hours. At the reference level (an average depth of 25.7 m and temperature of 15.7 ºC), the immediate survival was 99.9% (95% CI: 97.9 to 100%), but the estimated post-release survival decreased to 47.2% (33.8 to 65.8%). Relative post-release mortality doubled when the water temperature increased by 2.8 ºC or when the fishing depth increased up to 32 m. Furthermore, the swimming speed of the target species was significantly correlated with the estimated post-release survival; thus, this vitality metric may offer a promising strategy for more easily estimating post-release mortality in other fisheries., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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13. Mutations in the mitochondrial complex I assembly factor NDUFAF6 cause isolated bilateral striatal necrosis and progressive dystonia in childhood.
- Author
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Baide-Mairena H, Gaudó P, Marti-Sánchez L, Emperador S, Sánchez-Montanez A, Alonso-Luengo O, Correa M, Grau AM, Ortigoza-Escobar JD, Artuch R, Vázquez E, Del Toro M, Garrido-Pérez N, Ruiz-Pesini E, Montoya J, Bayona-Bafaluy MP, and Pérez-Dueñas B
- Subjects
- Biopsy, Child, Cohort Studies, Female, Fibroblasts, Gene Expression, Genetic Variation, Humans, Leigh Disease complications, Male, Muscles pathology, Mutation, Pedigree, Siblings, Striatonigral Degeneration genetics, Dystonic Disorders genetics, Electron Transport Complex I genetics, Leigh Disease genetics, Mitochondrial Proteins genetics, Striatonigral Degeneration congenital
- Abstract
Aim: To perform a deep phenotype characterisation in a pedigree of 3 siblings with Leigh syndrome and compound heterozygous NDUFAF6 mutations., Method: A multi-gene panel of childhood-onset basal ganglia neurodegeneration inherited conditions was analysed followed by functional studies in fibroblasts., Results: Three siblings developed gait dystonia in infancy followed by rapid progression to generalised dystonia and psychomotor regression. Brain magnetic resonance showed symmetric and bilateral cytotoxic lesions in the putamen and proliferation of the lenticular-striate arteries, latter spreading to the caudate and progressing to cavitation and volume loss. We identified a frameshift novel change (c.554_558delTTCTT; p.Tyr187AsnfsTer65) and a pathogenic missense change (c.371T>C; p.Ile124Thr) in the NDUFAF6 gene, which segregated with an autosomal recessive inheritance within the family. Patient mutations were associated with the absence of the NDUFAF6 protein and reduced activity and assembly of mature complex I in fibroblasts. By functional complementation assay, the mutant phenotype was rescued by the canonical version of the NDUFAF6. A literature review of 14 NDUFAF6 patients showed a consistent phenotype of an early childhood insidious onset neurological regression with prominent dystonia associated with basal ganglia degeneration and long survival., Interpretation: NDUFAF6-related Leigh syndrome is a relevant cause of childhood onset dystonia and isolated bilateral striatal necrosis. By genetic complementation, we could demonstrate the pathogenicity of novel genetic variants in NDUFAF6., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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14. Multiscale seascape habitat of necto-benthic littoral species, application to the study of the dusky grouper habitat shift throughout ontogeny.
- Author
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Alvarez-Berastegui D, Coll J, Rueda L, Stobart B, Morey G, Navarro O, Aparicio-González A, Grau AM, and Reñones O
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- Animals, Conservation of Natural Resources, Mediterranean Sea, Bass, Biodiversity, Ecosystem
- Abstract
Describing the spatial patterns of benthic coastal habitats and investigating how those patterns affect the ecology of inhabiting species is a main objective of seascape ecology. Within this emerging discipline spatial scale is a principal topic. Different spatial scales inform on different characteristics of the habitat and therefore the relation between species and their habitats would be better defined when observed at multiple levels of spatial scale. Here we apply a multiscale seascape approach to investigate the habitat preferences of juvenile and adult individuals of dusky grouper (Epinephelus marginatus) in a Mediterranean marine protected area. Results show that the information obtained at different spatial scales is complementary, improving our capability to identify the preferred habitats and how it changes throughout ontogeny. These results show the relevance of implementing multiscale seascape ecology approaches to investigate the species-habitat relationships and to improve management and conservation of necto-benthic endangered top predators., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2018
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15. Comparing the catch composition, profitability and discard survival from different trammel net designs targeting common spiny lobster ( Palinurus elephas ) in a Mediterranean fishery.
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Catanese G, Hinz H, Gil MDM, Palmer M, Breen M, Mira A, Pastor E, Grau A, Campos-Candela A, Koleva E, Grau AM, and Morales-Nin B
- Abstract
In the Balearic Islands, different trammel net designs have been adopted to promote fisheries sustainability and reduce discards. Here, we compare the catch performance of three trammel net designs targeting the spiny lobster Palinurus elephas in terms of biomass, species composition and revenue from commercial catches and discards. Designs differ in the netting fiber type (standard polyfilament, PMF, or a new polyethylene multi-monofilament, MMF) and the use of a guarding net or greca , a mesh piece intended to reduce discards. Catches were surveyed by an on-board observer from 1,550 netting walls corresponding to 70 nets. The number of marketable species captured indicated that the lobster trammel net fishery has multiple targets, which contribute significantly to the total revenue. The discarded species ranged from habitat-forming species to elasmobranches, but the magnitude of gear-habitat interactions on the long term dynamics of benthos remains unclear. No relevant differences in revenue and weight of discards were detected after Bayesian analyses. However, the species composition of discards was different when using greca . Interestingly, high immediate survival was found for discarded undersized lobsters, while a seven day survival assessment, using captive observation, gave an asymptotic estimate of survival probability as 0.64 (95% CI [0.54-0.76]). Therefore, it is recommended that it would be beneficial for this stock if an exemption from the EU landing obligation regulation was sought for undersized lobsters in the Balearic trammel net fishery., Competing Interests: The authors declare that they have no competing interests.
- Published
- 2018
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16. Increasing Antioxidant Activity and Protein Digestibility in Phaseolus vulgaris and Avena sativa by Fermentation with the Pleurotus ostreatus Fungus.
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Espinosa-Páez E, Alanis-Guzmán MG, Hernández-Luna CE, Báez-González JG, Amaya-Guerra CA, and Andrés-Grau AM
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- Amino Acids chemistry, Amino Acids metabolism, Antioxidants metabolism, Avena metabolism, Carbohydrates chemistry, Dietary Proteins metabolism, Fermentation, Humans, Mycelium metabolism, Nutritive Value, Phaseolus metabolism, Polyphenols chemistry, Polyphenols metabolism, Seeds chemistry, Seeds metabolism, Tannins chemistry, Tannins metabolism, Antioxidants chemistry, Avena chemistry, Dietary Proteins chemistry, Phaseolus chemistry, Pleurotus metabolism
- Abstract
The aim of the research was to determine the impact of fermentation with Pleurotus ostreatus on kidney beans, black beans, and oats. The results indicate that the fungus has a positive effect on the substrates when compared to the controls. The antioxidant activity (39.5% on kidney beans and 225% on oats in relation to the controls) and content of total polyphenols (kidney beans three times higher regarding the controls) increased significantly by the presence of the fungus mycelium, even after simulated digestion. There was a significant increase in protein digestibility (from 39.99 to 48.13% in black beans, 44.06 to 69.01% in kidney beans, and 63.25 to 70.01% in oats) and a decrease of antinutrient tannins (from 65.21 to 22.07 mg in black beans, 35.54 to 23.37 in kidney beans, and 55.67 to 28.11 in oats) as well as an increase in the contents of some essential amino acids. Overall, this fermentation treatment with Pleurotus ostreatus improved the nutritional quality of cereals and legumes, making them potential ingredients for the elaboration and/or fortification of foods for human nutrition., Competing Interests: No potential conflict of interest was reported by the authors.
- Published
- 2017
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17. A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67.
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Jovanović B, Mayer IA, Mayer EL, Abramson VG, Bardia A, Sanders ME, Kuba MG, Estrada MV, Beeler JS, Shaver TM, Johnson KC, Sanchez V, Rosenbluth JM, Dillon PM, Forero-Torres A, Chang JC, Meszoely IM, Grau AM, Lehmann BD, Shyr Y, Sheng Q, Chen SC, Arteaga CL, and Pietenpol JA
- Subjects
- Adult, Cisplatin adverse effects, DNA Damage drug effects, Drug-Related Side Effects and Adverse Reactions genetics, Drug-Related Side Effects and Adverse Reactions pathology, Everolimus adverse effects, Female, High-Throughput Nucleotide Sequencing, Humans, Ki-67 Antigen genetics, Lymphocytes, Tumor-Infiltrating pathology, Middle Aged, Mutation, Neoplasm Staging, Paclitaxel adverse effects, Receptors, Androgen genetics, Treatment Outcome, Triple Negative Breast Neoplasms genetics, Triple Negative Breast Neoplasms pathology, Cisplatin administration & dosage, Everolimus administration & dosage, Paclitaxel administration & dosage, Triple Negative Breast Neoplasms drug therapy
- Abstract
Purpose: Because of inherent disease heterogeneity, targeted therapies have eluded triple-negative breast cancer (TNBC), and biomarkers predictive of treatment response have not yet been identified. This study was designed to determine whether the mTOR inhibitor everolimus with cisplatin and paclitaxel would provide synergistic antitumor effects in TNBC. Methods: Patients with stage II/III TNBC were enrolled in a randomized phase II trial of preoperative weekly cisplatin, paclitaxel and daily everolimus or placebo for 12 weeks, until definitive surgery. Tumor specimens were obtained at baseline, cycle 1, and surgery. Primary endpoint was pathologic complete response (pCR); secondary endpoints included clinical responses, breast conservation rate, safety, and discovery of molecular features associated with outcome. Results: Between 2009 and 2013, 145 patients were accrued; 36% of patients in the everolimus arm and 49% of patients in the placebo arm achieved pCR; in each arm, 50% of patients achieved complete responses by imaging. Higher rates of neutropenia, mucositis, and transaminase elevation were seen with everolimus. Clinical response to therapy and long-term outcome correlated with increased frequency of DNA damage response (DDR) gene mutations, Basal-like1 and Mesenchymal TNBC-subtypes, AR-negative status, and high Ki67, but not with tumor-infiltrating lymphocytes. Conclusions: The paclitaxel/cisplatin combination was well tolerated and active, but addition of everolimus was associated with more adverse events without improvement in pCR or clinical response. However, discoveries made from correlative studies could lead to predictive TNBC biomarkers that may impact clinical decision-making and provide new avenues for mechanistic exploration that could lead to clinical utility. Clin Cancer Res; 23(15); 4035-45. ©2017 AACR ., (©2017 American Association for Cancer Research.)
- Published
- 2017
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18. Bilateral Changes in Deep Tissue Environment After Manual Lymphatic Drainage in Patients with Breast Cancer Treatment-Related Lymphedema.
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Donahue PM, Crescenzi R, Scott AO, Braxton V, Desai A, Smith SA, Jordi J, Meszoely IM, Grau AM, Kauffmann RM, Sweeting RS, Spotanski K, Ridner SH, and Donahue MJ
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- Adult, Axilla, Breast Cancer Lymphedema diagnosis, Breast Cancer Lymphedema etiology, Breast Neoplasms complications, Breast Neoplasms therapy, Case-Control Studies, Female, Humans, Lymph Node Excision adverse effects, Magnetic Resonance Imaging, Middle Aged, Treatment Outcome, Breast Cancer Lymphedema physiopathology, Breast Cancer Lymphedema therapy, Lymphatic Vessels physiopathology, Massage methods
- Abstract
Background: Breast cancer treatment-related lymphedema (BCRL) arises from a mechanical insufficiency following cancer therapies. Early BCRL detection and personalized intervention require an improved understanding of the physiological processes that initiate lymphatic impairment. Here, internal magnetic resonance imaging (MRI) measures of the tissue microenvironment were paired with clinical measures of tissue structure to test fundamental hypotheses regarding structural tissue and muscle changes after the commonly used therapeutic intervention of manual lymphatic drainage (MLD)., Methods and Results: Measurements to identify lymphatic dysfunction in healthy volunteers (n = 29) and patients with BCRL (n = 16) consisted of (1) limb volume, tissue dielectric constant, and bioelectrical impedance (i.e., non-MRI measures); (2) qualitative 3 Tesla diffusion-weighted, T
1 -weighted and T2 -weighted MRI; and (3) quantitative multi-echo T2 MRI of the axilla. Measurements were repeated in patients immediately following MLD. Normative control and BCRL T2 values were quantified and a signed Wilcoxon Rank-Sum test was applied (significance: two-sided p < 0.05). Non-MRI measures yielded significant capacity for discriminating between arms with versus without clinical signs of BCRL, yet yielded no change in response to MLD. Alternatively, a significant increase in deep tissue T2 on the involved (pre T2 = 0.0371 ± 0.003 seconds; post T2 = 0.0389 ± 0.003; p = 0.029) and contralateral (pre T2 = 0.0365 ± 0.002; post T2 = 0.0395 ± 0.002; p < 0.01) arms was observed. Trends for larger T2 increases on the involved side after MLD in patients with stage 2 BCRL relative to earlier stages 0 and 1 BCRL were observed, consistent with tissue composition changes in later stages of BCRL manifesting as breakdown of fibrotic tissue after MLD in the involved arm. Contrast consistent with relocation of fluid to the contralateral quadrant was observed in all stages., Conclusion: Quantitative deep tissue T2 MRI values yielded significant changes following MLD treatment, whereas non-MRI measurements did not vary. These findings highlight that internal imaging measures of tissue composition may be useful for evaluating how current and emerging therapies impact tissue function.- Published
- 2017
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19. Multiparametric magnetic resonance imaging for predicting pathological response after the first cycle of neoadjuvant chemotherapy in breast cancer.
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Li X, Abramson RG, Arlinghaus LR, Kang H, Chakravarthy AB, Abramson VG, Farley J, Mayer IA, Kelley MC, Meszoely IM, Means-Powell J, Grau AM, Sanders M, and Yankeelov TE
- Subjects
- Adult, Aged, Area Under Curve, Breast pathology, Contrast Media, Diffusion Magnetic Resonance Imaging, Female, Humans, Image Enhancement, Middle Aged, Reproducibility of Results, Sensitivity and Specificity, Treatment Outcome, Breast Neoplasms drug therapy, Magnetic Resonance Imaging, Neoadjuvant Therapy methods
- Abstract
Objectives: The purpose of this study was to determine whether multiparametric magnetic resonance imaging (MRI) using dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DWI), obtained before and after the first cycle of neoadjuvant chemotherapy (NAC), is superior to single-parameter measurements for predicting pathologic complete response (pCR) in patients with breast cancer., Materials and Methods: Patients with stage II/III breast cancer were enrolled in an institutional review board-approved study in which 3-T DCE-MRI and DWI data were acquired before (n = 42) and after 1 cycle (n = 36) of NAC. Estimates of the volume transfer rate (K), extravascular extracellular volume fraction (ve), blood plasma volume fraction (vp), and the efflux rate constant (kep = K/ve) were generated from the DCE-MRI data using the Extended Tofts-Kety model. The apparent diffusion coefficient (ADC) was estimated from the DWI data. The derived parameter kep/ADC was compared with single-parameter measurements for its ability to predict pCR after the first cycle of NAC., Results: The kep/ADC after the first cycle of NAC discriminated patients who went on to achieve a pCR (P < 0.001) and achieved a sensitivity, specificity, positive predictive value, and area under the receiver operator curve (AUC) of 0.92, 0.78, 0.69, and 0.88, respectively. These values were superior to the single parameters kep (AUC, 0.76) and ADC (AUC, 0.82). The AUCs between kep/ADC and kep were significantly different on the basis of the bootstrapped 95% confidence intervals (0.018-0.23), whereas the AUCs between kep/ADC and ADC trended toward significance (-0.11 to 0.24)., Conclusions: The multiparametric analysis of DCE-MRI and DWI was superior to the single-parameter measurements for predicting pCR after the first cycle of NAC.
- Published
- 2015
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20. DCE-MRI analysis methods for predicting the response of breast cancer to neoadjuvant chemotherapy: pilot study findings.
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Li X, Arlinghaus LR, Ayers GD, Chakravarthy AB, Abramson RG, Abramson VG, Atuegwu N, Farley J, Mayer IA, Kelley MC, Meszoely IM, Means-Powell J, Grau AM, Sanders M, Bhave SR, and Yankeelov TE
- Subjects
- Adult, Chemotherapy, Adjuvant methods, Female, Humans, Image Enhancement methods, Middle Aged, Neoadjuvant Therapy methods, Pilot Projects, Prognosis, Reproducibility of Results, Sensitivity and Specificity, Treatment Outcome, Antineoplastic Agents therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Image Interpretation, Computer-Assisted methods, Magnetic Resonance Imaging methods
- Abstract
Purpose: The purpose of this pilot study is to determine (1) if early changes in both semiquantitative and quantitative DCE-MRI parameters, observed after the first cycle of neoadjuvant chemotherapy in breast cancer patients, show significant difference between responders and nonresponders and (2) if these parameters can be used as a prognostic indicator of the eventual response., Methods: Twenty-eight patients were examined using DCE-MRI pre-, post-one cycle, and just prior to surgery. The semiquantitative parameters included longest dimension, tumor volume, initial area under the curve, and signal enhancement ratio related parameters, while quantitative parameters included K(trans), v(e), k(ep), v(p), and τ(i) estimated using the standard Tofts-Kety, extended Tofts-Kety, and fast exchange regime models., Results: Our preliminary results indicated that the signal enhancement ratio washout volume and k(ep) were significantly different between pathologic complete responders from nonresponders (P < 0.05) after a single cycle of chemotherapy. Receiver operator characteristic analysis showed that the AUC of the signal enhancement ratio washout volume was 0.75, and the AUCs of k(ep) estimated by three models were 0.78, 0.76, and 0.73, respectively., Conclusion: In summary, the signal enhancement ratio washout volume and k(ep) appear to predict breast cancer response after one cycle of neoadjuvant chemotherapy. This observation should be confirmed with additional prospective studies., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2014
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21. Mother-daughter communication about breast cancer risk: interpersonal and biological stress processes.
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Berlin KL, Andreotti C, Yull F, Grau AM, and Compas BE
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- Adolescent, Adult, Affect physiology, Age Factors, Child, Female, Humans, Middle Aged, Risk Factors, Saliva chemistry, Young Adult, Arousal physiology, Breast Neoplasms genetics, Breast Neoplasms psychology, Communication, Genetic Predisposition to Disease genetics, Genetic Predisposition to Disease psychology, Health Education, Hydrocortisone blood, Mother-Child Relations, Stress, Psychological complications
- Abstract
Women with a personal or maternal history of breast cancer experience psychological stress in relation to breast cancer risk, and adolescent and young adult daughters are particularly at risk for experiencing stress related to their mothers' history of breast cancer. The current study examined interpersonal and biological stress responses during a laboratory-based communication task about breast cancer risk in 32 mother-daughter dyads and explores whether certain communication styles between mothers and daughters are associated with increased stress reactivity during the task. Five saliva samples were collected from each participant to determine cortisol baseline levels, reactivity to, and recovery from the task. Negative maternal communication was associated with higher cortisol levels in daughters. In addition, maternal sadness was correlated with lower levels of daughters' cortisol at all time points with the exception of baseline measures. Implications for understanding the psychobiology of stress in women at risk for breast cancer are highlighted.
- Published
- 2013
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22. Juvenile fibroadenoma and granular cell tumor of the breast in an adolescent.
- Author
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Marshall AP, Spottswood SE, Grau AM, and Jackson GP
- Subjects
- Adolescent, Female, Humans, Breast Neoplasms pathology, Fibroadenoma pathology, Granular Cell Tumor pathology, Neoplasms, Multiple Primary pathology
- Abstract
We describe a case of a 15-year-old girl who presented with 2 painful masses in her right breast. Ultrasound confirmed the presence of 2 lesions, both of which appeared noncharacteristic for fibroadenomas. Both lesions were surgically resected. One was found to be a fibroadenoma and the other a granular cell tumor, both benign upon further histologic evaluation. Breast masses are rare in the pediatric population. The finding of a concurrent fibroadenoma and granular cell tumor is unique and has not been previously reported. Granular cell tumors of the breast are relatively uncommon. Often, they are mistaken for a breast malignancy. The concerning clinical and radiographic findings in this patient warranted operative excision., (Copyright © 2012 Elsevier Inc. All rights reserved.)
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- 2012
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23. Statistical comparison of dynamic contrast-enhanced MRI pharmacokinetic models in human breast cancer.
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Li X, Welch EB, Chakravarthy AB, Xu L, Arlinghaus LR, Farley J, Mayer IA, Kelley MC, Meszoely IM, Means-Powell J, Abramson VG, Grau AM, Gore JC, and Yankeelov TE
- Subjects
- Computer Simulation, Contrast Media pharmacokinetics, Data Interpretation, Statistical, Female, Humans, Image Enhancement methods, Models, Statistical, Reproducibility of Results, Sensitivity and Specificity, Breast Neoplasms metabolism, Breast Neoplasms pathology, Gadolinium DTPA pharmacokinetics, Image Interpretation, Computer-Assisted methods, Magnetic Resonance Imaging methods, Models, Biological
- Abstract
By fitting dynamic contrast-enhanced MRI data to an appropriate pharmacokinetic model, quantitative physiological parameters can be estimated. In this study, we compare four different models by applying four statistical measures to assess their ability to describe dynamic contrast-enhanced MRI data obtained in 28 human breast cancer patient sets: the chi-square test (χ(2)), Durbin-Watson statistic, Akaike information criterion, and Bayesian information criterion. The pharmacokinetic models include the fast exchange limit model with (FXL_v(p)) and without (FXL) a plasma component, and the fast and slow exchange regime models (FXR and SXR, respectively). The results show that the FXL_v(p) and FXR models yielded the smallest χ(2) in 45.64 and 47.53% of the voxels, respectively; they also had the smallest number of voxels showing serial correlation with 0.71 and 2.33%, respectively. The Akaike information criterion indicated that the FXL_v(p) and FXR models were preferred in 42.84 and 46.59% of the voxels, respectively. The Bayesian information criterion also indicated the FXL_v(p) and FXR models were preferred in 39.39 and 45.25% of the voxels, respectively. Thus, these four metrics indicate that the FXL_v(p) and the FXR models provide the most complete statistical description of dynamic contrast-enhanced MRI time courses for the patients selected in this study., (Copyright © 2011 Wiley Periodicals, Inc.)
- Published
- 2012
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24. Role for Rhizobium rhizogenes K84 cell envelope polysaccharides in surface interactions.
- Author
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Abarca-Grau AM, Burbank LP, de Paz HD, Crespo-Rivas JC, Marco-Noales E, López MM, Vinardell JM, von Bodman SB, and Penyalver R
- Subjects
- Antigens, Bacterial biosynthesis, Antigens, Surface biosynthesis, Gene Deletion, Genetic Complementation Test, O Antigens biosynthesis, Rhizobium metabolism, Bacterial Adhesion, Biofilms growth & development, Plant Roots microbiology, Polysaccharides, Bacterial metabolism, Rhizobium physiology
- Abstract
Rhizobium rhizogenes strain K84 is a commercial biocontrol agent used worldwide to control crown gall disease. The organism binds tightly to polypropylene substrate and efficiently colonizes root surfaces as complex, multilayered biofilms. A genetic screen identified two mutants in which these surface interactions were affected. One of these mutants failed to attach and form biofilms on the abiotic surface although, interestingly, it exhibited normal biofilm formation on the biological root tip surface. This mutant is disrupted in a wcbD ortholog gene, which is part of a large locus predicted to encode functions for the biosynthesis and export of a group II capsular polysaccharide (CPS). Expression of a functional copy of wcbD in the mutant background restored the ability of the bacteria to attach and form normal biofilms on the abiotic surface. The second identified mutant attached and formed visibly denser biofilms on both abiotic and root tip surfaces. This mutant is disrupted in the rkpK gene, which is predicted to encode a UDP-glucose 6-dehydrogenase required for O-antigen lipopolysaccharide (LPS) and K-antigen capsular polysaccharide (KPS) biosynthesis in rhizobia. The rkpK mutant from strain K84 was deficient in O-antigen synthesis and exclusively produced rough LPS. We also show that strain K84 does not synthesize the KPS typical of some other rhizobia strains. In addition, we identified a putative type II CPS, distinct from KPS, that mediates cell-surface interactions, and we show that O antigen of strain K84 is necessary for normal cell-cell interactions in the biofilms.
- Published
- 2012
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25. A novel AIF tracking method and comparison of DCE-MRI parameters using individual and population-based AIFs in human breast cancer.
- Author
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Li X, Welch EB, Arlinghaus LR, Chakravarthy AB, Xu L, Farley J, Loveless ME, Mayer IA, Kelley MC, Meszoely IM, Means-Powell JA, Abramson VG, Grau AM, Gore JC, and Yankeelov TE
- Subjects
- Algorithms, Breast Neoplasms diagnosis, Breast Neoplasms drug therapy, Computer Simulation, Female, Humans, Image Enhancement methods, Image Interpretation, Computer-Assisted methods, Reproducibility of Results, Sensitivity and Specificity, Axillary Artery physiopathology, Breast Neoplasms blood supply, Contrast Media pharmacokinetics, Gadolinium DTPA pharmacokinetics, Magnetic Resonance Imaging methods, Models, Biological, Perfusion Imaging methods
- Abstract
Quantitative analysis of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data requires the accurate determination of the arterial input function (AIF). A novel method for obtaining the AIF is presented here and pharmacokinetic parameters derived from individual and population-based AIFs are then compared. A Philips 3.0 T Achieva MR scanner was used to obtain 20 DCE-MRI data sets from ten breast cancer patients prior to and after one cycle of chemotherapy. Using a semi-automated method to estimate the AIF from the axillary artery, we obtain the AIF for each patient, AIF(ind), and compute a population-averaged AIF, AIF(pop). The extended standard model is used to estimate the physiological parameters using the two types of AIFs. The mean concordance correlation coefficient (CCC) for the AIFs segmented manually and by the proposed AIF tracking approach is 0.96, indicating accurate and automatic tracking of an AIF in DCE-MRI data of the breast is possible. Regarding the kinetic parameters, the CCC values for K(trans), v(p) and v(e) as estimated by AIF(ind) and AIF(pop) are 0.65, 0.74 and 0.31, respectively, based on the region of interest analysis. The average CCC values for the voxel-by-voxel analysis are 0.76, 0.84 and 0.68 for K(trans), v(p) and v(e), respectively. This work indicates that K(trans) and v(p) show good agreement between AIF(pop) and AIF(ind) while there is a weak agreement on v(e).
- Published
- 2011
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26. Motion correction in diffusion-weighted MRI of the breast at 3T.
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Arlinghaus LR, Welch EB, Chakravarthy AB, Xu L, Farley JS, Abramson VG, Grau AM, Kelley MC, Mayer IA, Means-Powell JA, Meszoely IM, Gore JC, and Yankeelov TE
- Subjects
- Adult, Algorithms, Artifacts, Breast Neoplasms pathology, Female, Humans, Image Processing, Computer-Assisted methods, Middle Aged, Models, Statistical, Motion, Principal Component Analysis, Breast pathology, Breast Neoplasms diagnosis, Diffusion Magnetic Resonance Imaging methods
- Abstract
Purpose: To provide a quantitative assessment of motion and distortion correction of diffusion-weighted images (DWIs) of the breast and to evaluate the effects of registration on the mean apparent diffusion coefficient (mADC)., Materials and Methods: Eight datasets from four patients with breast cancer and eight datasets from six healthy controls were acquired on a 3T scanner. A 3D affine registration was used to align each set of images and principal component analysis was used to assess the results. Variance in tumor ADC measurements, tumor mADC values, and voxel-wise tumor mADC values were compared before and after registration for each patient., Results: Image registration significantly (P = 0.008) improved image alignment for both groups and significantly (P < 0.001) reduced the variance across individual tumor ADC measurements. While misalignment led to potential under- and overestimation of mADC values for individual voxels, average tumor mADC values did not significantly change (P > 0.09) after registration., Conclusion: 3D affine registration improved the alignment of DWIs of the breast and reduced the variance between ADC measurements. Although the reduced variance did not significantly change tumor region-of-interest measures of mADC, it may have a significant impact on voxel-based analyses., (Copyright © 2011 Wiley-Liss, Inc.)
- Published
- 2011
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27. Differences in delta13C and delta15N stable isotopes in the pearly razorfish Xyrichtys novacula related to the sex, location and spawning period.
- Author
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Box A, Deudero S, Blanco A, Grau AM, and Riera F
- Subjects
- Animals, Body Size, Carbon Isotopes, Female, Gonads growth & development, Linear Models, Male, Mediterranean Sea, Nitrogen Isotopes, Carbon analysis, Nitrogen analysis, Perciformes physiology, Reproduction, Sex Characteristics
- Abstract
In the present study, Xyrichtys novacula (Labridae) were sampled at five locations around the islands of Ibiza and Formentera (western Mediterranean Sea). Isotopic signatures of delta13C, delta15N and the C:N ratio were analysed in relation to locality, sex and size differences. delta13C and delta15N partitioning was also studied in the reproductive spawning period. There were significant differences in the delta13C signature between localities for both sexes, but not for delta15N. Sex differences were also found with a mean +/-s.e. value of -17.38 +/- 0.06 per thousand delta13C and 8.36 +/- 0.05 per thousand delta(15)N for females and -17.17 +/- 0.07 per thousand delta13C and 8.80 +/- 0.06 per thousand delta15N for males. Increasing total length in both sexes was positively correlated with delta15N enrichment and a significant positive linear regression was established for both variables. During the reproductive spawning period, there were changes in delta13C fractioning with enrichment in postspawning females and males (with respect to prespawning and spawning periods) and delta(15)N impoverishment in postspawning females (with respect to prespawning and spawning periods). Xyrichtys novacula uses local food sources, as confirmed by delta(13)C and delta(15)N, and females and males use different food sources, thus avoiding intraspecific competition. This was confirmed by delta15N enrichment as size increased. Spawning leads to special requirements for gonad maturation, which is reflected in the isotopic signatures for both sexes.
- Published
- 2010
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28. Psychosocial determinants of mammography follow-up after receipt of abnormal mammography results in medically underserved women.
- Author
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Fair AM, Wujcik D, Lin JM, Zheng W, Egan KM, Grau AM, Champion VL, and Wallston KA
- Subjects
- Adult, Breast Neoplasms diagnostic imaging, Cohort Studies, Female, Health Services Accessibility, Humans, Middle Aged, Patient Acceptance of Health Care psychology, Retrospective Studies, Risk Factors, Rural Health, Socioeconomic Factors, Black or African American statistics & numerical data, Breast Neoplasms ethnology, Internal-External Control, Mammography statistics & numerical data, Patient Acceptance of Health Care ethnology, White People statistics & numerical data
- Abstract
This article targets the relationship between psychosocial determinants and abnormal screening mammography follow-up in a medically underserved population. Health belief scales were modified to refer to diagnostic follow-up versus annual screening. A retrospective cohort study design was used. Statistical analyses were performed examining relationships among sociodemographic factors, psychosocial determinants, and abnormal mammography follow-up. Women with lower mean internal health locus of control scores (3.14) were two times more likely than women with higher mean internal health locus of control scores (3.98) to have inadequate follow-up (OR=2.53, 95% CI=1.12-5.36). Women with less than a high school education had lower cancer fatalism scores than women who had completed high school (47.5 vs. 55.2, p-value=.02) and lower mean external health locus of control scores (3.0 vs. 5.3) (p-value<.01). These constructs have implications for understanding mammography follow-up among minority and medically underserved women. Further comprehensive study of these concepts is warranted.
- Published
- 2010
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29. [Acceptance of the HPV vaccine by parents of 11-year old girls].
- Author
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Armant FB, Arasanz ME, Grau AM, and Muñoz GT
- Subjects
- Child, Female, Humans, Attitude, Papillomavirus Vaccines, Parents, Uterine Cervical Neoplasms prevention & control
- Published
- 2009
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30. Circulating transforming growth factor-beta-1 and breast cancer prognosis: results from the Shanghai Breast Cancer Study.
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Grau AM, Wen W, Ramroopsingh DS, Gao YT, Zi J, Cai Q, Shu XO, and Zheng W
- Subjects
- Adult, Breast Neoplasms metabolism, Breast Neoplasms mortality, Case-Control Studies, China, Disease-Free Survival, Female, Humans, Middle Aged, Multivariate Analysis, Prognosis, Proportional Hazards Models, Protein Isoforms, Treatment Outcome, Breast Neoplasms blood, Breast Neoplasms diagnosis, Transforming Growth Factor beta1 blood
- Abstract
Introduction: Studies investigating the prognostic effect of circulating TGF-beta-1 in breast cancer have given inconsistent findings. The purpose of this study is to evaluate whether circulating transforming growth factor beta 1 (TGF-beta-1) is associated with overall and disease-free survival in a cohort of recently diagnosed breast cancer patients., Methods: We measured TGF-beta-1 levels in plasma samples of breast cancer patients in the Shanghai Breast Cancer Study, a population-based case-control study. We evaluated the relationship between TGF-beta-1 levels and overall and disease-free survival. The median follow up time was 7.2 years., Results: We observed that, compared with the patients with the lowest quartile of plasma TGF-beta-1, patients with the highest quartile of plasma TGF-beta-1 had significantly worse overall survival with hazards ratio (HR) = 2.78, with 95% confidence interval (CI): 1.34-5.79 and disease-free survival with HR = 2.49, 95% CI: 1.15-5.41, while the patients with the second and third quartiles of plasma TGF-beta-1 did not have significantly different overall and disease-free breast cancer survival. The shape of association between plasma TGF-beta-1 levels and breast cancer survival appears to be non-linear. Stratified analysis by stage of disease did not appreciably change the association pattern., Conclusions: We conclude that the relationship between circulating levels of TGF-beta-1 and prognosis in breast cancer is complex and non-linear. High levels of TGF-beta-1 are associated with worse survival independent of stage of disease.
- Published
- 2008
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31. Timing is everything: methodologic issues locating and recruiting medically underserved women for abnormal mammography follow-up research.
- Author
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Fair AM, Wujcik D, Lin JM, Egan KM, Grau AM, and Zheng W
- Subjects
- Adult, Black or African American statistics & numerical data, Aged, Breast Neoplasms prevention & control, Case-Control Studies, Female, Follow-Up Studies, Humans, Mass Screening, Middle Aged, Surveys and Questionnaires, Time Factors, United States, White People statistics & numerical data, Breast Neoplasms diagnosis, Mammography, Medically Underserved Area, Minority Groups, Patient Selection, Research Design
- Abstract
Objectives: Recruiting underserved women in breast cancer research studies remains a significant challenge. We present our experience attempting to locate and recruit minority and medically underserved women identified in a Nashville, Tennessee public hospital for a mammography follow-up study., Study Design: The study design was a retrospective hospital-based case-control study., Methods: We identified 227 women (88 African-American, 65 Caucasian, 36 other minority, 38 race undocumented in the medical record) who had undergone screening mammography and received an abnormal result during 2003-2004. Of the 227 women identified, 159 women were successfully located with implementation of a tracking protocol and more rigorous attempts to locate the women using online directory assistance and public record search engines. Women eligible for the study were invited to participate in a telephone research survey. Study completion was defined as fully finishing the telephone survey., Results: An average of 4.6 telephone calls (range 1-19) and 2.7 months (range 1-490 days) were required to reach the 159 women contacted. Within three contact attempts, more cases were located than controls (61% cases vs. 49% controls, p=0.03). African-American women cases were four times likely to be recruited than African-American controls, (OR, 4.07; 95% CI, 1.59-10.30) (p=0.003). After 3 months of effort, we located 67% of African-American women, 63% of Caucasian women, and 56% of other minorities. Ultimately, after a maximum of 12 attempts to contact women, 77% of African-American women and 71% of Caucasian women were eventually found. Of these, 59% of African-American women, 69% Caucasian women, and 50% other minorities were located and completed the study survey for an overall response rate of 59%, 71%, and 47% respectively., Conclusions: Data collection and study recruitment efforts were more challenging in racial and ethnic minorities. Continuing attempts to contact women may increase minority group study participation but does not guarantee retention or study completion.
- Published
- 2008
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32. Gastroduodenal artery pseudoaneurysm associated with hemosuccus pancreaticus and obstructive jaundice.
- Author
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Bohl JL, Dossett LA, and Grau AM
- Subjects
- Adult, Bile Ducts, Extrahepatic pathology, Bile Ducts, Intrahepatic pathology, Dilatation, Pathologic, Embolization, Therapeutic, Humans, Male, Pancreaticoduodenectomy, Recurrence, Aneurysm, False complications, Duodenum blood supply, Gastrointestinal Hemorrhage etiology, Jaundice, Obstructive complications, Pancreatic Ducts, Stomach blood supply
- Abstract
A 42-year-old male was admitted with recurrent gastrointestinal bleeding and new-onset jaundice. Computed tomography showed a persistent gastroduodenal artery pseudoaneurysm and dilated intrahepatic and extrahepatic ducts consistent with obstructive jaundice. This patient had two previous coil embolizations, which failed to prevent recurrent bleeding. The patient underwent pancreaticoduodenectomy for definitive treatment of his pseudoaneurysm. We report this case and review the literature.
- Published
- 2007
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33. Temporal trends of metals in benthic invertebrate species from the Balearic Islands, Western Mediterranean.
- Author
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Deudero S, Box A, March D, Valencia JM, Grau AM, Tintore J, and Benedicto J
- Subjects
- Animals, Environmental Monitoring, Mediterranean Sea, Arsenic metabolism, Bivalvia metabolism, Metals, Heavy metabolism, Sea Urchins metabolism, Water Pollutants, Chemical metabolism
- Published
- 2007
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34. Organic compounds temporal trends at some invertebrate species from the Balearics, Western Mediterranean.
- Author
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Deudero S, Box A, March D, Valencia JM, Grau AM, Tintore J, Calvo M, and Caixach J
- Subjects
- Animals, Invertebrates classification, Mediterranean Region, Time Factors, Water Pollution, Chemical, DDT analysis, Hexachlorobenzene analysis, Hexachlorocyclohexane analysis, Invertebrates chemistry, Polychlorinated Biphenyls analysis, Water Pollutants, Chemical analysis
- Abstract
Concentrations of persistent organic pollutants (POPs) such as hexachlorobenzene (HCB), dichlore diphenyl trichloretane (DDT), polychlorinated biphenyls (PCBs), and gamma-hexachlorocyclohexane (gamma-HCH or lindane) were determined in tissue of marine benthic invertebrates such as Mytilus galloprovincialis, Chamelea gallina, Venus verrucosa, Lithophaga lithophaga and Paracentrotus lividus. Species were selected due to their habitat, trophic level, feeding behaviour and their consumption. Invertebrate species were systematically sampled from December 1996 to December 2005 from several sites along the Balearic Islands. The highest concentrations of PCBs (785ng/g lipid) were found in M. galloprovincialis while the lowest concentrations were found in the sea-urchin P. lividus (193ng/g lipid). Among the 7 PCB quantified congeners the higher values are mainly obtained for CB138 and CB153. All bivalves presented higher PCBs contents than the sea-urchin P. lividus are possibly linked with the bioaccumulation process of POPs throughout the food web and to differential detoxifying mechanisms. The concentration of SigmaDDT exceeds that of HCB and gamma-HCH at all species and sampling stations. DDT concentrations ranged from 0.4ng/g ww at the bivalve C. gallina in 2002, to values of 15.8ng/g ww at the bivalve L. lithophaga in 1998. The values obtained for the organic compounds (HCH, HCB, PCBs, DDT) depend upon the place and year of sampling and are compared to values found by other authors for the mussel M. galloprovincialis in other Mediterranean areas. gamma-HCH and HCB were found in lower concentrations than the other POPs.
- Published
- 2007
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35. Role of Smad proteins in the regulation of NF-kappaB by TGF-beta in colon cancer cells.
- Author
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Grau AM, Datta PK, Zi J, Halder SK, and Beauchamp RD
- Subjects
- Active Transport, Cell Nucleus, Activin Receptors, Type I metabolism, Animals, Cell Line, Tumor, Cell Nucleus metabolism, Colonic Neoplasms, DNA metabolism, Enzyme Activation, Epithelial Cells metabolism, Humans, I-kappa B Kinase metabolism, Phosphorylation, Protein Binding, Protein Serine-Threonine Kinases, Receptor, Transforming Growth Factor-beta Type I, Receptors, Transforming Growth Factor beta metabolism, Signal Transduction, Smad7 Protein biosynthesis, Smad7 Protein genetics, Transcriptional Activation, Transforming Growth Factor beta1, NF-kappa B metabolism, Smad4 Protein physiology, Smad7 Protein physiology, Transforming Growth Factor beta physiology
- Abstract
Nuclear factor kappa B (NF-kappaB) has been implicated in cancer cell survival. We explored the role of the TGF-beta pathway in the regulation of NF-kappaB in colon cancer cells. TGF-beta-1 treatment of the colon adenocarcinoma cell line FET-1, results in an early increase in IkappaB-alpha phosphorylation that precedes NF-kappaB nuclear translocation and DNA binding activity. Activation of the TGF-beta type I receptor is required for the TGF-beta-mediated activation of NF-kappaB. No activation of NF-kappaB is observed in a Smad4 null cell line, SW480, even though TGF-beta does result in IkappaB-alpha phosphorylation in these cells. Smad4 restores the TGF-beta-1-mediated NF-kappaB activation in SW480 cells. TGF-beta-1 treatment fails to activate NF-kappaB or phosphorylate IkappaB-alpha in FET-1 cells expressing the inhibitory Smad, Smad7. Taken together, these results suggest a role for Smad4 in the transcriptional activation of NF-kappaB, and a direct effect of Smad 7 inhibiting IkappaB-alpha phosphorylation rather than through the well-established inhibition of Smad2/3 phosphorylation with subsequent inhibition of the TGF-beta pathway.
- Published
- 2006
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36. Transduodenal excision of bleeding periampullary endocrine tumor as a bridge to pancreaticoduodenectomy in a Jehovah's Witness patient.
- Author
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Grau AM and Ballard BR
- Subjects
- Blood Loss, Surgical, Blood Transfusion, Common Bile Duct Neoplasms diagnostic imaging, Humans, Male, Middle Aged, Tomography, X-Ray Computed, Treatment Refusal, Ampulla of Vater, Common Bile Duct Neoplasms surgery, Jehovah's Witnesses, Pancreaticoduodenectomy methods
- Abstract
We discuss the case of a Jehovah's Witness patient who presented with a bleeding endocrine periampullary mass. Transduodenal excision of the ampullary mass was successfully performed as a bridge to pancreaticoduodenectomy in this critically ill patient. The roles of pancreaticoduodenectomy and alternatives to pancreaticoduodenectomy in the emergency setting are reviewed, in particular, for patients who decline transfusion of blood products. The surgical approach to surgery and perioperative anemia in Jehovah's Witness patients is described. Finally, we reviewed the role of transduodenal excision in the management of ampullary tumors and describe its use as a bridge to pancreaticoduodenectomy in a patient with a malignant neoplasm of the ampulla.
- Published
- 2006
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37. Neoadjuvant concurrent paclitaxel and radiation in stage II/III breast cancer.
- Author
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Chakravarthy AB, Kelley MC, McLaren B, Truica CI, Billheimer D, Mayer IA, Grau AM, Johnson DH, Simpson JF, Beauchamp RD, Jones C, and Pietenpol JA
- Subjects
- Adult, Aged, Biomarkers, Tumor metabolism, Combined Modality Therapy, Female, Gamma Rays, Humans, Middle Aged, Neoplasm Staging, Radiotherapy Dosage, Antineoplastic Agents, Phytogenic therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms radiotherapy, Breast Neoplasms surgery, Neoadjuvant Therapy, Paclitaxel therapeutic use
- Abstract
Purpose: The aim of this study was to determine the safety and pathologic response rates following neoadjuvant paclitaxel and radiation in patients with stage II/III breast cancer and to evaluate the use of sequential biopsies to allow an in vivo assessment of biological markers as potential predictive markers of response to this regimen., Patients and Methods: Patients with high-risk, operable breast cancer were treated with three cycles of paclitaxel 175 mg/m2 every 3 weeks, followed by twice-weekly paclitaxel 30 mg/m2 and concurrent radiation. Core biopsies were obtained at baseline and 24 to 72 hours after the first cycle of paclitaxel. After completing neoadjuvant treatment, patients underwent definitive surgery. The primary end point was pathologic complete response, which is defined as the absence of any invasive cancer at surgery. Potential markers of therapeutic response were evaluated including markers of proliferation, apoptosis, p21, HER2, estrogen receptor, and progesterone receptor status., Results: Of the 38 patients enrolled, 13 (34%) had a pathologic complete response. There was no significant difference in baseline Ki-67 between responders (35%) and nonresponders (28%; P = 0.45). There was also no significant change in Ki-67 following paclitaxel administration. Despite this lack of immunohistologic change in proliferative activity, baseline mitotic index was higher for patients with pathologic complete response over nonresponders (27 versus 10, P = 0.003). Moreover, the increase in mitotic index following paclitaxel administration was associated with pathologic complete response., Conclusions: Neoadjuvant paclitaxel/radiation is effective and well tolerated. Tumor proliferation at baseline and response to chemotherapy as measured by mitotic activity may serve as an important indicator of pathologic response to neoadjuvant paclitaxel/radiation.
- Published
- 2006
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38. Colorectal cancer prevention: adherence patterns and correlates of tests done for screening purposes within United States populations.
- Author
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Ata A, Elzey JD, Insaf TZ, Grau AM, Stain SC, and Ahmed NU
- Subjects
- Black or African American statistics & numerical data, Aged, Aged, 80 and over, Colorectal Neoplasms diagnosis, Colorectal Neoplasms ethnology, Female, Health Behavior ethnology, Health Planning Guidelines, Health Surveys, Hispanic or Latino statistics & numerical data, Humans, Male, Middle Aged, United States epidemiology, White People statistics & numerical data, Colonoscopy statistics & numerical data, Colorectal Neoplasms prevention & control, Mass Screening statistics & numerical data, Occult Blood, Sigmoidoscopy statistics & numerical data
- Abstract
Background: Studies exploring CRC testing prevalence and correlates within US populations have provided limited and sometimes conflicting information. The most recent national-level reports have described US usage of CRC tests but none have considered only those tests done specifically for screening reasons as an outcome variable., Methods: Using the NHIS 2000 sample of >or=50 year-old, we assessed screening behavior using an outcome variable accounting for (1) any combination of recommended tests (2) done within their respective time guidelines, and (3) specifically for screening purposes., Results: Only 25.8% (95% CI: 24.9-26.7%) of the population reported getting a test done for screening purposes within the recommended time. Most (>85%) of the FOBTs and only about 60% of endoscopies were done for screening. Among those who had an endoscopy within the recommended time, Blacks were more likely than Whites to report screening as the purpose of the test. Hispanics had the lowest test usage irrespective of test time, reason or type. Hispanics were 50% (p<0.001) less likely to be adherent, and Blacks approximately 22% (p<0.01) less likely to be adherent, than Whites. After multivariate adjustment, differences between Whites and Blacks disappeared; Hispanics remained less likely. Increasing education predicted higher adherence among Whites but only undergraduate completion did so among Blacks. Male gender predicted adherence only among Blacks and insurance only among Hispanics., Conclusions: Preventive screening for CRC is lower than estimates from previous studies. Future studies should consider accounting for test purpose. Our findings need confirmation through studies based on objective data.
- Published
- 2006
- Full Text
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39. Effect of race on long-term survival of breast cancer patients: transinstitutional analysis from an inner city hospital and university medical center.
- Author
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Grau AM, Ata A, Foster L, Ahmed NU, Gorman DR, Shyr Y, Stain SC, and Pearson AS
- Subjects
- Academic Medical Centers statistics & numerical data, Disease-Free Survival, Female, Follow-Up Studies, Hospitals, University statistics & numerical data, Hospitals, Urban statistics & numerical data, Humans, Longitudinal Studies, Neoplasm Staging, Prognosis, Retrospective Studies, Social Class, Survival Rate, Tennessee epidemiology, Treatment Outcome, Black or African American, Black People statistics & numerical data, Breast Neoplasms mortality, White People statistics & numerical data
- Abstract
Black women have the highest mortality for breast cancer. Our hypothesis is that racial disparities in breast cancer survival persist after controlling for stage of disease and treatment at both a city hospital as well as at a university hospital. Data from tumor registries of breast cancer patients at a city hospital and a university center were analyzed for overall and disease-specific survival, controlling for stage and treatment. Black patients presented with more advanced stages and had significantly worse survival compared with whites. After controlling for stage of disease and treatment, a difference in survival persisted for stage II patients, with blacks doing worse than whites at both institutions. Although there were socioeconomic differences, race was an independent prognostic factor, with black patients having the worse prognosis. The lower survival of black women with breast cancer is only partially explained by their advanced stage at diagnosis. Black women with potentially curable stage II cancer had a lower survival that is not explained by the variables measured.
- Published
- 2005
40. Malignant phyllodes tumor of the breast: review of the literature and case report of stromal overgrowth.
- Author
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Guerrero MA, Ballard BR, and Grau AM
- Subjects
- Aged, Aged, 80 and over, Breast Neoplasms epidemiology, Breast Neoplasms pathology, Female, Humans, Phyllodes Tumor epidemiology, Phyllodes Tumor pathology, Treatment Outcome, Breast Neoplasms surgery, Phyllodes Tumor surgery
- Abstract
Cystosarcoma phyllodes constitutes only 0.3-0.9% of all breast tumors. The term "sarcoma" was initially used because of its fleshy appearance, a more modern term is Phyllodes tumor (PT). The behavior of PT constitutes a spectrum from benign and locally recurrent to malignant and metastatic. In a general surgical series, 6.2% of the tumors were malignant. The microscopic appearance of PT is that of epithelial elements and connective tissue stroma. Malignancy is determined by characteristics of the stroma. The metastatic spread of malignant PT is mainly hematogenous to lung, with infrequent lymphatic involvement. Wide local excision with 2 cm margins is the treatment of choice. In 20% of both benign and malignant cases, PT will locally recur. There is no proven benefit of radiation or chemotherapy, although radiotherapy may be useful in selected cases. We present a case of a sarcomatous overgrowth in a malignant phyllodes tumor involving multiple histologic types.
- Published
- 2003
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41. Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration in patients with presumed pancreatic cancer.
- Author
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Raut CP, Grau AM, Staerkel GA, Kaw M, Tamm EP, Wolff RA, Vauthey JN, Lee JE, Pisters PWT, and Evans DB
- Subjects
- Humans, Predictive Value of Tests, Sensitivity and Specificity, Biopsy, Needle, Endosonography, Pancreas pathology, Pancreatic Neoplasms diagnosis
- Abstract
Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of the pancreas allows the diagnosis of pancreatic cancer to be established without exploratory surgery. We reviewed our recent experience with EUS-FNA in patients with presumed pancreatic cancer and report the diagnostic accuracy and complications of this procedure. Data were reviewed from all patients who presented with CT evidence of a pancreatic mass or a malignant biliary stricture and underwent EUS-FNA at our institution between November 1, 1999, and October 1, 2001. Based on the findings of contrast-enhanced, multislice CT scanning, patients were categorized as having resectable, locally advanced, or metastatic disease. EUS-FNA was performed in 233 patients. A final diagnosis of cancer was established in 216 patients (93%), 15 patients (6%) were found to have benign disease, and the final diagnosis remains unknown in two patients (1%). The sensitivity, specificity, and accuracy of EUS-FNA for diagnosis of a pancreatic malignancy were 91%, 100%, and 92%, respectively. For the 216 patients subsequently proven to have cancer, the results of EUS-FNA were diagnostic in 197 (91%); 96 (90%) of 107 patients with resectable disease, 62 (97%) of 64 with locally advanced disease, and 39 (87%) of 45 with metastatic disease. Four patients (2%) developed a clinically apparent complication that required hospital admission, including two patients who required surgery for duodenal perforation. There were no EUS-related deaths. We conclude that EUS-FNA can safely and accurately establish a cytologic diagnosis in patients with both early-stage and advanced pancreatic cancer. This enables consideration of all treatment options including protocol-based therapy., (Copyright 2003 The Society for Surgery of the Alimentary Tract, Inc.)
- Published
- 2003
- Full Text
- View/download PDF
42. Colonic adenocarcinoma in a congenital rectourethral fistula in association with high imperforate anus and multiple genitourinary anomalies.
- Author
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Clark T, Riordan W, Grau AM, Dave DS, Roberts RL, and Smith ER Jr
- Subjects
- Adenocarcinoma diagnostic imaging, Adenocarcinoma pathology, Colonic Neoplasms diagnostic imaging, Colonic Neoplasms pathology, Humans, Male, Middle Aged, Radiography, Rectal Fistula complications, Urethral Diseases complications, Urinary Fistula complications, Adenocarcinoma complications, Anus, Imperforate complications, Colonic Neoplasms complications, Rectal Fistula congenital, Urethral Diseases congenital, Urinary Fistula congenital, Urogenital Abnormalities complications
- Published
- 2002
- Full Text
- View/download PDF
43. Suppression of tumorigenesis and induction of p15(ink4b) by Smad4/DPC4 in human pancreatic cancer cells.
- Author
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Peng B, Fleming JB, Breslin T, Grau AM, Fojioka S, Abbruzzese JL, Evans DB, Ayers D, Wathen K, Wu T, Robertson KD, and Chiao PJ
- Subjects
- Adenoviridae genetics, Animals, Blotting, Northern, Blotting, Western, Cell Cycle Proteins metabolism, Cell Division, Cell Nucleus metabolism, Cyclin-Dependent Kinase Inhibitor p15, Cyclin-Dependent Kinase Inhibitor p16 metabolism, Cyclin-Dependent Kinase Inhibitor p21, Cyclins metabolism, Gene Deletion, Genes, Reporter, Homozygote, Humans, Immunoblotting, Luciferases metabolism, Mice, Mice, Nude, Neoplasm Transplantation, Promoter Regions, Genetic, Signal Transduction, Smad4 Protein, Time Factors, Transcriptional Activation, Transfection, Transforming Growth Factor beta metabolism, Tumor Cells, Cultured, Cell Cycle Proteins pharmacology, Cyclin-Dependent Kinase Inhibitor p16 pharmacology, DNA-Binding Proteins metabolism, Pancreatic Neoplasms metabolism, Trans-Activators metabolism, Tumor Suppressor Proteins
- Abstract
Purpose: The tumor suppressor gene Smad4/DPC4, a key transcription factorin transforming growth factor beta (TGF-beta) signaling cascades,is inactivated in 50% of pancreatic adenocarcinomas. We seek to determine the role of Smad4/DPC4 in the suppression of tumor cell growth and in the regulation of TGF-beta-mediated expression of cell-cycle regulatory genes p15(ink4b) and p21(waf1)., Experimental Design: Smad4/DPC4 is overexpressed by adenoviral infection in CFPac-1 pancreatic cancer cells, in which the Smad4/DPC4 is homozygously deleted, and in Capan-1 pancreatic cancer cells, in which Smad4/DPC4 is not expressed. Expression of the TGF-beta downstream target gene p21(waf1), regulation of the p15(ink4b) promoter, anchorage-independent growth, and tumorigenesis were examined., Results: We demonstrate that expression of Smad4/DPC4 in Capan-1 cells reduced anchorage-independent growth by more than 50%, and inhibited xenograft tumor growth. However, overexpression of Smad4/DPC4 did not inhibit CFPac-1 cell growth. Interestingly, Smad4/DPC4 induced expression of p15(ink4b), p21(waf1), and TGF-beta-responsive reporter gene in Capan-1 but not in CFPac-1 cells. Furthermore, we found a previously unidentified Smad4 binding element (SBE) located in the region between -356 and -329 bp of the p15(ink4b) promoter. The p15(ink4b) promoter reporter gene assays revealed that Smad4-dependent transcriptional activation is mediated by this SBE, which indicates that p15(ink4b) is one of the downstream target genes regulated by Smad/DPC4., Conclusion: These results explain the role of Smad4/DPC4 in TGF-beta-mediated inhibition of cell proliferation in vitro and in vivo. Moreover, these results suggest that Smad4/DPC4-mediated tumor suppression and induction of TGF-beta-regulated cell-cycle-inhibitory genes may depend on additional factors that are absent in CFPac-1 cells.
- Published
- 2002
44. Tumor suppressor gene Smad4/DPC4, its downstream target genes, and regulation of cell cycle.
- Author
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Chiao PJ, Hunt KK, Grau AM, Abramian A, Fleming J, Zhang W, Breslin T, Abbruzzese JL, and Evans DB
- Subjects
- Cell Cycle physiology, Cell Division drug effects, Cyclin-Dependent Kinase Inhibitor p21, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Humans, Smad4 Protein, Trans-Activators genetics, Trans-Activators metabolism, Transforming Growth Factor beta pharmacology, Tumor Cells, Cultured, Adenocarcinoma genetics, Cyclins genetics, DNA-Binding Proteins physiology, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Pancreatic Neoplasms genetics, Signal Transduction, Trans-Activators physiology, Transforming Growth Factor beta metabolism
- Abstract
The tumor suppressor gene deleted in pancreatic cancer locus 4 (Smad4/DPC4) is inactivated in about 50% of pancreatic adenocarcinomas. The role of DPC4 in the transforming growth factor-beta (TGF-beta) receptor-mediated signal transduction cascade in human pancreatic, colon, and breast carcinoma cell lines has been investigated by a number of laboratories. The results demonstrate that Smad4/DPC4 protein functions as a key transcription factor required in regulation of TGF-beta inducible gene expression and subsequent growth inhibition. Many transcription regulators that are involved in cell growth, differentiation, and oncogenesis have been identified and cloned. Yet paradoxically, it is much more difficult to identify the important downstream target genes responsible for the biological effects elicited by these transcription factors. Although numerous attempts have been made and different approaches have been used to identify the target genes, only limited success has been achieved. Our data show that p21waf1 is one of the Smad4/DPC4-regulated downstream target genes and suggest that overexpression of the Smad4/DPC4 gene can bypass TGF-beta receptor activation and reestablish one of the key regulatory controls of cell proliferation. Identification of the Smad-regulated downstream target genes responsible for diverse biological processes that they control will extend our understanding of the mechanism for cell cycle regulation and cell differentiation.
- Published
- 1999
- Full Text
- View/download PDF
45. Prognostic factors in resectable pancreatic cancer: p53 and bcl-2.
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Bold RJ, Hess KR, Pearson AS, Grau AM, Sinicrope FA, Jennings M, McConkey DJ, Bucana CD, Cleary KR, Hallin PA, Chiao PJ, Abbruzzese JL, and Evans DB
- Subjects
- Adenocarcinoma pathology, Analysis of Variance, Apoptosis genetics, Cell Cycle genetics, Cell Nucleus ultrastructure, Coloring Agents, Combined Modality Therapy, Female, Forecasting, Gene Expression Regulation, Neoplastic genetics, Genes, bcl-2 genetics, Genes, p53 genetics, Humans, Immunohistochemistry, Male, Middle Aged, Multivariate Analysis, Neoplasm Staging, Pancreatic Neoplasms pathology, Pancreaticoduodenectomy, Prognosis, Prospective Studies, Proto-Oncogene Mas, Survival Rate, Adenocarcinoma surgery, Biomarkers, Tumor analysis, Pancreatic Neoplasms surgery, Proto-Oncogene Proteins c-bcl-2 analysis, Tumor Suppressor Protein p53 analysis
- Abstract
The p53 tumor suppressor gene and the Bcl-2 proto-oncogene regulate cell cycle progression and apoptosis. We evaluated the expression of these molecular markers with standard pathologic prognostic variables in patients who received multimodality therapy for resectable adenocarcinoma of the pancreas to study the effect of p53 and Bcl-2 on survival duration. Immunohistochemical staining of archival material was performed to determine levels of expression of p53 and Bcl-2 proteins in 70 patients with adenocarcinoma of pancreatic origin. All patients underwent a potentially curative pancreaticoduodenectomy and standardized pathologic analysis of resected specimens. Potential pathologic and molecular prognostic variables were assessed for their effect on survival duration. Nuclear staining for p53 was observed in 33 (47%) of 70 specimens. Immunostaining for Bcl-2 was observed in 23 specimens (33%). A trend toward improved survival duration was seen in patients whose tumors stained positive for either p53 or Bcl-2. Negative staining for both markers predicted short survival (P = 0.01). By univariate and multivariate analyses, no single pathologic factor was associated with survival duration. Immunohistochemical staging using both p53 and Bcl-2 significantly predicted survival duration by univariate and multivariate analysis; patients whose tumors stained positively for p53 and/or overexpressed Bcl-2 had a significantly longer survival than those whose tumors stained negative for both proteins.
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- 1999
- Full Text
- View/download PDF
46. Cell cycle regulation of human pancreatic cancer by tamoxifen.
- Author
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Robinson EK, Grau AM, Evans DB, Smid CM, Chiao PJ, Abbruzzese JL, and Grimm EA
- Subjects
- Antineoplastic Agents, Hormonal pharmacology, Apoptosis, Cell Division drug effects, Cyclin-Dependent Kinase Inhibitor p21, Cyclins genetics, Flow Cytometry, Humans, RNA, Messenger analysis, RNA, Neoplasm analysis, Tamoxifen pharmacology, Tumor Cells, Cultured, Antineoplastic Agents, Hormonal therapeutic use, Cell Cycle drug effects, Cyclins biosynthesis, Gene Expression Regulation drug effects, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology, Tamoxifen therapeutic use
- Abstract
Background: Clinical trials have suggested a survival advantage for selected patients with metastatic pancreatic cancer treated with tamoxifen. We sought to identify the molecular mechanism by which tamoxifen inhibits human pancreatic cancer cell (HPCC) growth., Methods: HPCCs were grown in tamoxifen and growth inhibition was determined by 3H-thymidine uptake and by the MTT assay; changes in cell viability were determined by cell counts. Cell cycle alterations were evaluated by FACS, and the induction of apoptosis was evaluated using the TUNEL assay. Total cellular RNA was isolated after tamoxifen treatment, and Northern blot analysis was performed for p21waf1., Results: Tamoxifen inhibited HPCC growth as measured by inhibition of 3H-thymidine incorporation and by the MTT assay. However, there was no decrease in the total number of viable cells after 6 days of treatment with 10 microM of tamoxifen and no evident apoptosis, confirming the absence of a cytotoxic effect. Cell cycle analysis revealed cellular arrest in the G0/G1 phase, which correlated with p21waf1 mRNA upregulation in response to tamoxifen treatment., Conclusions: Tamoxifen inhibits HPCC growth by inducing G0/G1 arrest with an associated increase in p21waf1 mRNA expression. Tamoxifen is an effective inhibitor of HPCC growth in vitro and warrants further in vivo study.
- Published
- 1998
- Full Text
- View/download PDF
47. Induction of p21waf1 expression and growth inhibition by transforming growth factor beta involve the tumor suppressor gene DPC4 in human pancreatic adenocarcinoma cells.
- Author
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Grau AM, Zhang L, Wang W, Ruan S, Evans DB, Abbruzzese JL, Zhang W, and Chiao PJ
- Subjects
- Adenocarcinoma pathology, Cell Division, Cyclin-Dependent Kinase Inhibitor p21, Gene Expression Regulation, Neoplastic, Humans, Pancreatic Neoplasms pathology, RNA, Messenger genetics, RNA, Neoplasm genetics, Smad4 Protein, Tumor Cells, Cultured, Adenocarcinoma genetics, Cyclins genetics, DNA-Binding Proteins, Genes, Tumor Suppressor, Pancreatic Neoplasms genetics, Trans-Activators physiology, Transforming Growth Factor beta physiology
- Abstract
The tumor suppressor gene deleted in pancreatic cancer locus 4 (DPC4) is inactivated in about 50% of pancreatic adenocarcinomas. DPC4 was found to be homologous to Smad4 and may function as a transcription factor in the transforming growth factor beta (TGF-beta) receptor-mediated signal transduction pathway. We have investigated the role of DPC4 in the TGF-beta receptor-mediated signal transduction cascade in five human pancreatic cancer cell lines (Panc-1, MDAPanc-28, HS766T, Capan-1, and MiaPaCa-2). Our results demonstrate that the loss of responsiveness to TGF-beta-induced growth inhibition correlates with the loss of expression of DPC4. We have shown that TGF-beta induces p21waf1 expression in Panc-1 cells, whereas no induction of p21waf1 expression by TGF-beta was detected in the other four cell lines lacking either DPC4 expression or the TGF-beta type II receptor. No increase in p21waf1 mRNA stability was observed after treatment with TGF-beta, which suggests that the induction of p21waf1 in Panc-1 cells is transcriptionally regulated by TGF-beta. Our data also demonstrate that the expression of DPC4 is directly involved in TGF-beta-mediated induction of the 3TP-lux reporter gene, which contains a known TGF-beta-inducible plasminogen activator inhibitor promoter. These data suggest that: (a) TGF-beta-mediated induction of p21waf1 and subsequent growth inhibition require the expression of DPC4; (b) p21waf1 is a downstream target gene of DPC4; and (c) transfection of the DPC4 gene restores the TGF-beta-inducible gene expression. Inactivation of the tumor suppressor gene DPC4 and other components of the TGF-beta signal cascades may abolish one of the key negative controls of cell proliferation in pancreatic adenocarcinomas.
- Published
- 1997
48. Peroxisomal fatty acid oxidation and inhibitors of the mitochondrial carnitine palmitoyltransferase I in isolated rat hepatocytes.
- Author
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Skorin C, Necochea C, Johow V, Soto U, Grau AM, Bremer J, and Leighton F
- Subjects
- Animals, Carnitine Acyltransferases antagonists & inhibitors, Carnitine Acyltransferases metabolism, Carnitine O-Acetyltransferase antagonists & inhibitors, Carnitine O-Acetyltransferase metabolism, Carnitine O-Palmitoyltransferase antagonists & inhibitors, Cells, Cultured, Chlorpromazine pharmacology, Epoxy Compounds pharmacology, Fatty Acids pharmacology, Hydrogen Peroxide metabolism, Ketones metabolism, Male, Oxidation-Reduction, Palmitates metabolism, Rats, Rats, Inbred Strains, Carnitine O-Palmitoyltransferase metabolism, Fatty Acids metabolism, Microbodies metabolism, Mitochondria, Liver enzymology
- Abstract
Fatty acid oxidation was studied in the presence of inhibitors of carnitine palmitoyltransferase I (CPT I), in normal and in peroxisome-proliferated rat hepatocytes. The oxidation decreased in mitochondria, as expected, but in peroxisomes it increased. These two effects were seen, in variable proportions, with (+)-decanoylcarnitine, 2-tetradecylglycidic acid (TDGA) and etomoxir. The decrease in mitochondrial oxidation (ketogenesis) affected saturated fatty acids with 12 or more carbon atoms, whereas the increase in peroxisomal oxidation (H2O2 production) affected saturated fatty acids with 8 or more carbon atoms. The peroxisomal increase was sensitive to chlorpromazine, a peroxisomal inhibitor. To study possible mechanisms, palmitoyl-, octanoyl- and acetyl-carnitine acyltransferase activities were measured, in homogenates and in subcellular fractions from control and TDGA-treated cells. The palmitoylcarnitine acyltransferase was inhibited, as expected, but the octanoyltransferase activity also decreased. The CoA derivative of TDGA was synthesized and tentatively identified as being responsible for inhibition of the octanoylcarnitine acyltransferase. These results show that inhibitors of the mitochondrial CPT I may also inhibit the peroxisomal octanoyl transferase; they also support the hypothesis that the octanoyltransferase has the capacity to control or regulate peroxisomal fatty acid oxidation.
- Published
- 1992
- Full Text
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49. [Radiation enteritis: the results of surgical treatment].
- Author
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López F, Grau AM, Méndez A, and Zúñiga A
- Subjects
- Adult, Aged, Aged, 80 and over, Chile epidemiology, Enteritis epidemiology, Enteritis etiology, Enteritis mortality, Female, Follow-Up Studies, Humans, Male, Middle Aged, Postoperative Complications epidemiology, Postoperative Complications mortality, Radiation Injuries epidemiology, Radiation Injuries etiology, Radiation Injuries mortality, Radiotherapy adverse effects, Radiotherapy Dosage, Retrospective Studies, Risk Factors, Enteritis surgery, Radiation Injuries surgery
- Abstract
We reviewed the results of surgical therapy for radiation enteropathy in 18 consecutive patients. Fifteen (83%) were females and the age ranged from 31 to 81 years old. The indication for radiotherapy was cancer of the cervix in 10 patients (56). The mean radiation dose was 5190 rads (range 4000 to 7000). Of 23 radiation lesions, 12 (52%) were located in the ileon, 10 in the rectum and 1 in the sigmoid. Fibrosis and stenosis was the most frequent lesion (70%) followed by fistulae (22%) and proctitis in 2 patients. Resection or derivation was the surgical treatment employed in 22 of the 23 lesions. For lesions of the ileon, we performed resection and anastomosis in 7 patients and derivation in 5. For rectal lesions we performed resection, endoanal descent and colo-anal anastomosis in 7 patients anterior resection in 2 and colostomy in 1. Complications were observed in 5 patients (28%) and 1 patient died (5%). After a mean follow up of 56 months, 5 patients have died from recurrence of the original neoplastic lesions. We feel that surgical treatment allows improvement in quality of life of patients with radiation enteropathy.
- Published
- 1990
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