104 results on '"Lemay R"'
Search Results
2. Fabry Disease in Latin America: Data from the Fabry Registry
- Author
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Villalobos, J., Politei, J. M., Martins, A. M., Cabrera, G., Amartino, H., Lemay, R., Ospina, S., Ordoñez, S. Suarez, Varas, C., Zschocke, Johannes, editor, Gibson, K Michael, editor, Brown, Garry, editor, Morava, Eva, editor, and Peters, Verena, editor
- Published
- 2013
- Full Text
- View/download PDF
3. Fabry Disease in Latin America: Data from the Fabry Registry
- Author
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Villalobos, J., primary, Politei, J. M., additional, Martins, A. M., additional, Cabrera, G., additional, Amartino, H., additional, Lemay, R., additional, Ospina, S., additional, Ordoñez, S. Suarez, additional, and Varas, C., additional
- Published
- 2012
- Full Text
- View/download PDF
4. Steady-state kinetic studies with the polysulfonate U-9843, an HIV reverse transcriptase inhibitor
- Author
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Althaus, I. W., Chou, J. J., Gonzales, A. J., LeMay, R. J., Deibel, M. R., Chou, K. -C., Kezdy, F. J., Romero, D. L., Thomas, R. C., Aristoff, P. A., Tarpley, W. G., and Reusser, F.
- Published
- 1994
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5. Enzymatic kinetic studies with the non-nucleoside HIV reverse transcriptase inhibitor U-9843
- Author
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Althaus, I. W., LeMay, R. J., Gonzales, A. J., Deibel, M. R., Sharma, S. K., Kezdy, F. J., Resnick, L., Busso, M. E., Aristoff, P. A., and Reusser, F.
- Published
- 1992
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6. Seedling growth and development on space shuttle
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Cowles, J, Lemay, R, and Jahns, G
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Life Sciences (General) - Abstract
Young pine seedlings, and mung bean and oat seeds were flown on shuttle flights, STS-3 and STS-51F, in March, 1982 and July/August, 1985, respectively. The plant growth units built to support the two experiments functioned mechanically as anticipated and provided the necessary support data. Pine seedlings exposed to the microgravity environment of the space shuttle for 8 days continued to grow at a rate similar to ground controls. Pine stems in flight seedlings, however, averaged 10 to 12% less lignin than controls. Flight mung beans grew slower than control beans and their stems contained about 25% less lignin than control seedlings. Reduced mung bean growth in microgravity was partly due to slower germination rate. Lignin also was reduced in flight oats as compared to controls. Oats and mung beans exhibited upward growing roots which were not observed in control seedlings. Chlorophyll A/B ratios were lower in flight tissues than controls. The sealed PGCs exhibited large variations in atmospheric gas composition but the changes were similar between flight and ground controls. Ethylene was present in low concentrations in all chambers.
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- 1994
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7. Growth and Lignification in Seedlings Exposed to Eight Days of Microgravity
- Author
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COWLES, J. R., SCHELD, H. W., LEMAY, R., and PETERSON, C.
- Published
- 1984
8. L'ISLAM HISTORIQUE ET LES SCIENCES OCCULTES
- Author
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Lemay, R.
- Published
- 1992
9. Lignification in Young Plant Seedlings Grown on Earth and Aboard the Space Shuttle
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Cowles, Joe R., primary, LeMay, R., additional, Jahns, G., additional, Scheld, W. H., additional, and Peterson, C., additional
- Published
- 1989
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10. Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation
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Warnock, D G, Ortiz, A, Mauer, M, Linthorst, G E, Oliveira, J P, Serra, A L, Marodi, L, Mignani, R, Vujkovac, B, Beitner-Johnson, D, Lemay, R, Cole, J A, Svarstad, E, Waldek, S, Germain, D P, Wanner, C, Warnock, D G, Ortiz, A, Mauer, M, Linthorst, G E, Oliveira, J P, Serra, A L, Marodi, L, Mignani, R, Vujkovac, B, Beitner-Johnson, D, Lemay, R, Cole, J A, Svarstad, E, Waldek, S, Germain, D P, and Wanner, C
- Abstract
BACKGROUND: The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta. METHODS: Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment. Multivariate logistic regression analyses were used to identify factors associated with renal disease progression. RESULTS: Men within the first quartile had a mean eGFR slope of -0.1 mL/min/1.73m(2)/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of -6.7 mL/min/1.73m(2)/year. The risk factor most strongly associated with renal disease progression was averaged urinary protein:creatinine ratio (UP/Cr) ≥1 g/g (odds ratio 112, 95% confidence interval (95% CI) 4-3109, P = 0.0054). Longer time from symptom onset to treatment was also associated with renal disease progression (odds ratio 19, 95% CI 2-184, P = 0.0098). Women in Quartile 4 had the highest averaged UP/Cr (mean 1.8 g/g) and the most rapid renal disease progression: (mean slope -4.4 mL/min/1.73m(2)/year). CONCLUSIONS: Adults with Fabry disease are at risk for progressive loss of eGFR despite enzyme replacement therapy, particularly if proteinuria is ≥1 g/g. Men with little urinary protein excretion and those who began receiving agalsidase beta sooner after the onset of symptoms had stable renal function. These findings suggest that early intervention may lead to optimal renal outcomes.
- Published
- 2012
11. P24—Prognostic Indicators of Renal Disease Progression: Natural History Data From the Fabry Registry
- Author
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Wanner, C., primary, Oliveira, J.P., additional, Ortiz, A., additional, Mauer, M., additional, Germain, D.P., additional, Linthorst, G.E., additional, Serra, A.L., additional, Maródi, L., additional, Mignani, R., additional, Cianciaruso, B., additional, Vujkovac, B., additional, Lemay, R., additional, Beitner-Johnson, D., additional, Waldek, S., additional, and Warnock, D.G., additional
- Published
- 2012
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12. P1-12-12: Evaluation of Ile655Val HER2 Polymorphism Associated with Cardiac Toxicity Following the Administration of Trastuzumab in Women with Non-Metastatic Breast Cancer.
- Author
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Diorio, C, primary, Lemieux, J, additional, Côté, M-A, additional, Provencher, L, additional, Nadeau-Larochelle, C, additional, Jacob, S, additional, Demers, É, additional, Tremblay-Lemay, R, additional, Saint-Pierre, C, additional, Beauchemin, M, additional, Barabé, F, additional, and Laflamme, C, additional
- Published
- 2011
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13. Lignification in young plant seedlings grown on earth and aboard the Space Shuttle
- Author
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Cowles, Joe R, Lemay, R, Jahns, G, Scheld, W. H, and Peterson, C
- Subjects
Man/System Technology And Life Support - Abstract
The Space Shuttle era has provided an opportunity for investigators to conduct experiments in a microgravity environment. Two Shuttle flights, STS-3 and STS-51F, each contained an experiment designed principally to determine whether young plant seedlings exposed to microgravity had reduced lignin content in comparison to seedlings grown at one gravity. Three different plant species, pine, oats, and mung beans, were exposed for eight days to the microgravity environment of the Shuttle. The lignin content of in-flight seedlings was less than the control seedlings in all seven sets of seedlings included in these two experiments. In five sets of seedlings, the reduction in lignin content in flight seedlings ranged from 6 to 24 percent and was statistically significant. In addition, the activity of two enzymes involved in lignin synthesis, phenylalanine ammonia lyase and peroxidase, were significantly reduced in pine seedlings. It was therefore concluded that microgravity, as perceived by young plant seedlings, results in reduced lignin synthesis.
- Published
- 1989
14. Growth and development of plants flown on the STS-3 Space Shuttle mission
- Author
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Cowles, J. R, Scheld, H. W, Peterson, C, and Lemay, R
- Subjects
Life Sciences (General) - Abstract
Pre-germinated pine seedlings and germinating oat and mung bean seeds were flown on the STS-3 Space Shuttle mission. Overall, the seedlings grew and developed well in space. Some oat and mung bean roots, however, grew upward. Lignin content was slightly lower in flight tissues and protein content was higher.
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- 1984
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15. Prevention of Radiation-enhancement Dermatitis and Breast Cancer Cell Invasion by an Anti-Inflammatory Agent
- Author
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Lemay, R., primary, Tremblay, L., additional, Archambault, M., additional, Lepage, M., additional, and Paquette, B., additional
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- 2008
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16. In vitro irradiation of basement membrane enhances the invasiveness of breast cancer cells
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Paquette, B, primary, Baptiste, C, additional, Therriault, H, additional, Arguin, G, additional, Plouffe, B, additional, and Lemay, R, additional
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- 2007
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17. The attached processor for speech.
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Hochgesang, G., Lemay, R., and Silverman, H.
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- 1980
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18. A Modification of the NOCOLOK™ Flux Brazing Process to Produce Superior Corrosion Resistance or Black Surfaces.
- Author
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McCubbin, J. G., primary and Lemay, R., additional
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- 1990
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19. In Vitro Generation of Peroxynitrite by 2- and 4-Hydroxyestrogens in the Presence of Nitric Oxide
- Author
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Paquette, B., Cantin, A. M., Kocsis-Bedard, S., Barry, S., Lemay, R., and Jay-Gerin, J.-P.
- Abstract
Estrogen metabolism is altered in most, if not all, breast cancer tumors. These alterations primarily lead to the formation of the catechol estrogen metabolites, 2- and 4-hydroxyestrogens, which can generate superoxide anion radicals (O
2 •-) through the redox cycling of semiquinone/quinone derivatives. In breast cancer cells, the activity of nitric oxide synthase is also frequently elevated, resulting in an increased level of exposure to nitric oxide (•NO). Since •NO rapidly reacts with O2 •- to produce the peroxynitrite anion (ONOO-), this study was undertaken to determine whether ONOO-2 ) gave an optimal ONOO- production of 11.9 ± 1.9 μM (mean ± SD). Quantification of ONOO- was not modified by mannitol, supporting the idea that the hydroxyl radical was not involved. This production of ONOO-2 was saturated. The excess of •NO would probably react with aqueous oxygen to form nitrite (NO2 -). Since the third-order reaction rate for the reaction between 2•NO and O2 is 2 × 106 M-2 s-1, it can therefore be suggested that the reaction between •NO and 4-OHE2 occurs at a faster rate.- Published
- 2001
20. Progress toward the Development of a Safe and Effective Agent for Treating Reentrant Cardiac Arrhythmias: Synthesis and Evaluation of Ibutilide Analogues with Enhanced Metabolic Stability and Diminished Proarrhythmic Potential
- Author
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Hester, J. B., Gibson, J. K., Buchanan, L. V., Cimini, M. G., Clark, M. A., Emmert, D. E., Glavanovich, M. A., Imbordino, R. J., LeMay, R. J., McMillan, M. W., Perricone, S. C., Squires, D. M., and Walters, R. R.
- Abstract
A series of ibutilide analogues with fluorine substituents on the heptyl side chain was prepared and evaluated for class III antiarrhythmic activity, metabolic stability, and proarrhythmic potential. It was found that fluorine substituents stabilized the side chain to metabolic oxidation. Many of the compounds also retained the ability to increase the refractoriness of cardiac tissue at both slow and fast pacing rates. The potential for producing polymorphic ventricular tachycardia in the rabbit model was dependent on the chirality of the benzylic carbon. The S-enantiomers generally had less proarrhythmic activity than the corresponding racemates. One compound from this series (
45E , trecetilide fumarate) had excellent antiarrhythmic activity and metabolic stability and was devoid of proarrhythmic activity in the rabbit model. It was chosen for further development.- Published
- 2001
21. The Benzylthio-Pyrimidine U-31,355, a Potent Inhibitor of HIV-1 Reverse Transcriptase
- Author
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Althaus, I. W., Chou, K.-C., Lemay, R. J., Franks, K. M., Deibel, M. R., Kezdy, F. J., Resnick, L., Busso, M. E., So, A. G., and Downey, K. M.
- Published
- 1996
- Full Text
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22. The influence of potassium sulphate impurity on thermal reactions between aluminum and potassium fluorides
- Author
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Ross, R.A., primary, East, F., additional, Lemay, R., additional, and Takacs, A.M., additional
- Published
- 1986
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23. Hydration effects in reactions between aluminum and potassium fluorides
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Ross, R.A., primary, East, F., additional, Cooney, C.B., additional, Heier, S., additional, Lemay, R., additional, and Takacs, A.M., additional
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- 1986
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24. ChemInform Abstract: Hydration Effects in Reactions Between Aluminum and Potassium Fluorides.
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ROSS, R. A., primary, EAST, F., additional, COONEY, C. B., additional, HEIER, S., additional, LEMAY, R., additional, and TAKACS, A. M., additional
- Published
- 1986
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25. 550. Attitudes of nurses, physicians and pharmacists toward a unit dose drug distribution system
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SIMON, J. R., primary, LEMAY, R. P., additional, and TESTER, W. W., additional
- Published
- 1968
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26. The attached processor for speech
- Author
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Hochgesang, G., primary, Lemay, R., additional, and Silverman, H., additional
- Full Text
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27. Using technology to improve patient collections.
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Newland K and LeMay R
- Published
- 2008
28. Prognostic indicators of renal disease progression in adults with Fabry disease: natural history data from the Fabry Registry
- Author
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Stephen Waldek, Christoph Wanner, Alberto Ortiz, Michael Mauer, Gabor E. Linthorst, Dominique P. Germain, Andreas L. Serra, Dana Beitner-Johnson, David G. Warnock, Renzo Mignani, Roberta Lemay, Bruno Cianciaruso, João Paulo Oliveira, Bojan Vujkovac, László Maródi, Endocrinology, Wanner, C, Oliveira, Jp, Ortiz, A, Mauer, M, Germain, Dp, Linthorst, Ge, Serra, Al, Maródi, L, Mignani, R, Cianciaruso, Bruno, Vujkovac, B, Lemay, R, Beitner Johnson, D, Waldek, S, and Warnock, Dg
- Subjects
Adult ,Male ,medicine.medical_specialty ,Epidemiology ,Urinary system ,Urology ,Renal function ,Critical Care and Intensive Care Medicine ,Klinikai orvostudományok ,Excretion ,chemistry.chemical_compound ,renal disease ,Internal medicine ,medicine ,Humans ,Enzyme Replacement Therapy ,Registries ,Transplantation ,Creatinine ,Proteinuria ,business.industry ,Fabry Registry ,Enzyme replacement therapy ,Original Articles ,Orvostudományok ,Middle Aged ,medicine.disease ,Prognosis ,Fabry disease ,Natural history ,Endocrinology ,chemistry ,Nephrology ,Disease Progression ,Fabry Disease ,Kidney Failure, Chronic ,Female ,Kidney Diseases ,medicine.symptom ,business ,Glomerular Filtration Rate - Abstract
Background and objectives: These analyses were designed to characterize renal disease progression in untreated adults with Fabry disease. Design, setting, participants, & measurements: Data from the Fabry Registry for 462 untreated adults (121 men and 341 women) who had at least two estimated GFR (eGFR) values over a span of ≥12 months before starting enzyme replacement therapy were included. Results: Most men (86 of 121, 71%) had more rapid loss of kidney function than the normal adult population (loss of eGFR > −1 ml/min per 1.73 m2 per year), whereas fewer women (133 of 341, 39%) had rapid loss of kidney function. Patients with rapid progression had significantly higher mean averaged urinary protein to urinary creatinine ratios (UP/Cr) than patients with slower progression (1.5 versus 0.2 for men; 1.4 versus 0.5 for women; P < 0.0001). Patients were grouped into quartiles based on averaged UP/Cr; renal function in men declined more rapidly with higher UP/Cr, with the steepest declines observed in men with UP/Cr > 1.5 (mean eGFR slope, −5.6 ml/min per 1.73 m2 per year; n = 30). eGFR slope declined more slowly in women, with the steepest declines observed in women with UP/Cr > 1.2 (mean eGFR slope, −1.3 ml/min per 1.73 m2 per year; n = 85). Regression models of eGFR slope indicated that UP/Cr is the most important indicator of renal disease progression in adult Fabry patients. In women, lower baseline eGFR and age were also associated with renal disease progression. Women who had clinical events had more rapid loss of kidney function. Conclusions: Urinary protein excretion is strongly associated with renal disease progression in men and women with Fabry disease.
- Published
- 2010
29. Single gene mutations and prognosis in limited-stage follicular lymphoma treated with radiation therapy.
- Author
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Hershenfeld SA, Tobin JWD, Shelton V, Calvente L, Lajkosz K, Liu T, Brodtkorb M, d'Amore FA, Ludvigsen M, Baetz T, LeBrun D, Johnson N, Crump M, Hong M, Kuruvilla J, Tremblay-LeMay R, MacManus M, Tsang R, Hodgson DC, Gandhi MK, and Kridel R
- Abstract
Radiotherapy is routinely used for management of limited-stage follicular lymphoma (FL), yet half of patients ultimately relapse. We hypothesized that the presence of specific gene mutations may predict outcomes. We performed targeted sequencing of a 69-gene panel in 117 limited-stage FL patients treated with radiotherapy and identified recurrently mutated genes. CREBBP was most frequently mutated, and mutated CREBBP was associated with inferior progression-free survival, though not after false discovery rate adjustment. This association failed to validate in an independent cohort. We conclude that recurrent gene mutations do not predict outcomes in this setting. Alternative biomarkers may offer better prognostic insight., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2024
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30. Identification of genetic subtypes in follicular lymphoma.
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Shelton V, Detroja R, Liu T, Isaev K, Silva A, Passerini V, Bakhtiari M, Calvente L, Hong M, He MY, Modi S, Hershenfeld SA, Ludvigsen M, Madsen C, Hamilton-Dutoit S, d'Amore FA, Brodtkorb M, Johnson NA, Baetz T, LeBrun D, Tobin JWD, Gandhi MK, Mungall AJ, Xu W, Ben-Neriah S, Steidl C, Delabie J, Tremblay-LeMay R, Jegede O, Weigert O, Kahl B, Evens AM, and Kridel R
- Subjects
- Humans, Female, Male, Mutation, Middle Aged, Aged, Biomarkers, Tumor genetics, Prognosis, Lymphoma, Follicular genetics, Lymphoma, Follicular pathology
- Abstract
Follicular lymphoma (FL) exhibits considerable variability in biological features and clinical trajectories across patients. To dissect the diversity of FL, we utilized a Bernoulli mixture model to identify genetic subtypes in 713 pre-treatment tumor tissue samples. Our analysis revealed the existence of five subtypes with unique genetic profiles that correlated with clinicopathological characteristics. The clusters were enriched in specific mutations as follows: CS (CREBBP and STAT6), TT (TNFAIP3 and TP53), GM (GNA13 and MEF2B), Q (quiescent, for low mutation burden), and AR (mutations of mTOR pathway-related genes). The subtype Q was enriched for patients with stage I disease and associated with a lower proliferative history than the other subtypes. The AR subtype was unique in its enrichment for IgM-expressing FL cases and was associated with advanced-stage and more than 4 nodal sites. The existence of subtypes was validated in an independent cohort of 418 samples from the GALLIUM trial. Notably, patients assigned to the TT subtype consistently experienced inferior progression-free survival when treated with immunochemotherapy. Our findings offer insight into core pathways distinctly linked with each FL cluster and are expected to be informative in the era of targeted therapies., (© 2024. The Author(s).)
- Published
- 2024
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31. RUNX1 mutations correlate with response to venetoclax combination therapies in relapsed/refractory acute myeloid leukemia.
- Author
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Chow S, Tang K, Al-Abri M, Hall V, Tremblay-Lemay R, Rashedi I, Tsui H, and Chan SM
- Subjects
- Azacitidine administration & dosage, Bridged Bicyclo Compounds, Heterocyclic administration & dosage, Combined Modality Therapy, Decitabine administration & dosage, Female, Follow-Up Studies, Humans, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy, Male, Middle Aged, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local therapy, Prognosis, Retrospective Studies, Sulfonamides administration & dosage, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation mortality, Core Binding Factor Alpha 2 Subunit genetics, Drug Resistance, Neoplasm, Leukemia, Myeloid, Acute pathology, Mutation, Neoplasm Recurrence, Local pathology
- Published
- 2021
- Full Text
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32. DNA Methylation-Based Classification of Small B-Cell Lymphomas: A Proof-of-Principle Study.
- Author
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Xia D, Leon AJ, Yan J, Silva A, Bakhtiari M, Tremblay-LeMay R, Selvarajah S, Sabatini P, Diamandis P, Pugh T, Kridel R, and Delabie J
- Subjects
- Aged, Biomarkers, Tumor genetics, Female, Humans, Lymph Nodes pathology, Lymphoma, B-Cell classification, Lymphoma, B-Cell surgery, Lymphoma, B-Cell, Marginal Zone genetics, Lymphoma, B-Cell, Marginal Zone surgery, Middle Aged, Models, Biological, Proof of Concept Study, Reproducibility of Results, DNA Methylation, Lymphoma, B-Cell genetics, Lymphoma, B-Cell pathology
- Abstract
Although most small B-cell lymphomas (SBCLs) can be diagnosed using routine methods, challenges exist. For example, marginal zone lymphomas (MZLs) can be difficult to rule-in, in large part because no widely-used, sensitive, and specific biomarker is available for the marginal zone cell of origin. In this study, it was hypothesized that DNA methylation array profiling can assist with the classification of SBCLs, including MZLs. Extramedullary SBCLs, including challenging cases, were reviewed internally for pathology consensus and profiled. By combining the resulting array data set with data sets from other groups, a set of 26 informative probes was selected and used to train machine learning models to classify 4 common SBCLs: chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, and MZL. Prediction probability cutoff was used to separate classifiable from unclassifiable cases, and show that the trained model was able to classify 95% of independent test cases (n = 264/279). The concordance between model predictions and pathology diagnoses was 99.6% (n = 262/263) among classifiable test cases. One validation reference test case was reclassified based on model prediction. The model was also used to predict the diagnoses of two challenging SBCLs. Although the differential examined and data on difficult cases are limited, these results support accurate methylation-based classification of SBCLs. Furthermore, high specificities of predictions suggest that methylation signatures can be used to rule-in MZLs., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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33. Breast implant-associated EBV-positive diffuse large B-cell lymphoma: Two case reports and literature review.
- Author
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Morgan S, Tremblay-LeMay R, Lipa JE, Sur M, Delabie J, Imrie K, Crump M, Snell LJ, and Ghorab Z
- Subjects
- Adult, Carcinoma, Lobular pathology, Female, Humans, Middle Aged, Neoplasms, Multiple Primary pathology, Breast Implants adverse effects, Breast Neoplasms etiology, Epstein-Barr Virus Infections complications, Lymphoma, Large B-Cell, Diffuse etiology
- Abstract
Lymphomas associated with breast implants are mostly of the T-cell type. They are predominantly anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK-negative ALCL) characterized by CD30 positivity universally. Whilst the majority of primary breast lymphomas occurring in the absence of breast implants are of B-cell origin, there are few cases of implant-associated B-cell lymphomas reported to date in the literature, a subset of which are diffuse large B-cell lymphoma (DLBCL). Given the rarity of this entity, we describe two cases of breast implant-associated DLBCL. Both patients developed Epstein-Barr Virus (EBV)-positive large cell lymphoma of B-cell origin confined to the implant capsule with no evidence of systemic lymphoma. Considering the association with EBV, the activated B-cell phenotype and the presumed chronic inflammatory environment associated with the implant capsule, these might represent forms of DLBCL associated with chronic inflammation (DLBCL-CI) or fibrin-associated DLBCL (FA-DLBCL). Treatment included implant removal with total capsulectomy, and for one of the cases adjuvant systemic chemotherapy. Recognizing this rare type of breast implant-associated B-cell lymphoma could improve our understanding of this entity and hence develop appropriate management strategies., (Copyright © 2021. Published by Elsevier GmbH.)
- Published
- 2021
- Full Text
- View/download PDF
34. Marginal zone lymphoma transdifferentiated to histiocytic sarcoma.
- Author
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Sabatini PJB, Tremblay-LeMay R, Ahmadi Moghaddam P, Delabie JMA, and Sakhdari A
- Subjects
- Antigens, CD analysis, B-Lymphocytes pathology, Female, Humans, Middle Aged, Histiocytic Sarcoma pathology, Lymphoma, B-Cell, Marginal Zone pathology
- Published
- 2021
- Full Text
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35. Molecular attributes underlying central nervous system and systemic relapse in diffuse large B-cell lymphoma.
- Author
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Isaev K, Ennishi D, Hilton L, Skinnider B, Mungall KL, Mungall AJ, Bakhtiari M, Tremblay-LeMay R, Silva A, Ben-Neriah S, Boyle M, Villa D, Marra MA, Steidl C, Gascoyne RD, Morin R, Savage KJ, Scott DW, and Kridel R
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Central Nervous System, Humans, Neoplasm Recurrence, Local drug therapy, Rituximab therapeutic use, Central Nervous System Neoplasms diagnosis, Central Nervous System Neoplasms drug therapy, Central Nervous System Neoplasms genetics, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics
- Published
- 2021
- Full Text
- View/download PDF
36. Validation of the RHL30 digital gene expression assay as a prognostic biomarker for relapsed Hodgkin lymphoma.
- Author
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Calvente L, Tremblay-LeMay R, Xu W, Chan FC, Hong M, Zhang T, Yhim HY, Kuruvilla J, Crump M, Kukreti V, Prica A, Regier D, Marra MA, Karsan A, Steidl C, Scott DW, Sabatini P, and Kridel R
- Subjects
- Adult, Autografts, Female, Humans, Male, Middle Aged, Risk Factors, Biomarkers, Tumor biosynthesis, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Hematopoietic Stem Cell Transplantation, Hodgkin Disease metabolism, Hodgkin Disease mortality, Hodgkin Disease therapy
- Abstract
Despite continuing improvements in the management of classical Hodgkin lymphoma (cHL), relapse remains associated with a risk of lymphoma-related mortality. The biological composition of relapse tumour biopsies shows interpatient variability, which can be leveraged to design prognostic biomarkers. Here, we validated the RHL30 assay, a previously reported gene expression model in an independent cohort of 41 patients with relapsed cHL. Patients classified as high-risk by the RHL30 assay had inferior failure-free survival (FFS) after autologous stem cell transplantation (2-year FFS 41% vs. 92%, P = 0·035). The RHL30 model is a robust biomarker that risk-stratifies patients considered for autologous stem cell transplantation., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2020
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37. Use of a rare disease registry for establishing phenotypic classification of previously unassigned GLA variants: a consensus classification system by a multispecialty Fabry disease genotype-phenotype workgroup.
- Author
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Germain DP, Oliveira JP, Bichet DG, Yoo HW, Hopkin RJ, Lemay R, Politei J, Wanner C, Wilcox WR, and Warnock DG
- Subjects
- Aged, Alleles, Fabry Disease pathology, Female, Genetic Association Studies, Genotype, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Mutation genetics, Phenotype, Polymorphism, Single Nucleotide genetics, Rare Diseases pathology, Registries, Fabry Disease genetics, Rare Diseases genetics, alpha-Galactosidase genetics
- Abstract
Background: Fabry disease (α-galactosidase deficiency) is an X-linked genetic disease caused by a variety of pathogenic GLA variants. The phenotypic heterogeneity is considerable, with two major forms, classic and later-onset disease, but adjudication of clinical phenotype is currently lacking for many variants. We aimed to determine consensus phenotypic classification for previously unclassified GLA variants from the GLA -specific fabry-database.org database., Methods: A Fabry disease genotype-phenotype workgroup developed a five-stage iterative system based on expert clinical assessment, published literature and clinical evidence of pathogenicity using a 2-point scoring system based on clinical hallmarks of classic disease. Kaplan-Meier (KM) analysis of severe clinical event-free survival was used as final validation. Results were compared with those from web-based disease databases and in silico pathogenicity prediction programmes., Results: Final consensus on classifications of 'pathogenic' was achieved for 32 of 33 GLA variants (26 'classic' phenotype, 171 males; 6 'later-onset' phenotype, 57 males). One variant remained of uncertain significance. KM curves were similar for the known fabry-database.org database phenotypes and when workgroup consensus classifications were added, and the curves retained the same separation between 'classic' and 'later-onset' phenotypes., Conclusion: The iterative system implemented by a Fabry disease genotype-phenotype workgroup achieved phenotypic classifications for variants that were previously unclassified. Clinical pathogenicity associated with a particular GLA variant defined in affected males appears to have predictive value and also generally correlates with risk for affected females. The newly established classifications can be of benefit to the clinical care of Fabry patients harbouring these variants., Competing Interests: Competing interests: DPG is a consultant for Sanofi Genzyme and Takeda/Shire, was an investigator in clinical trials sponsored by Amicus Therapeutics and Sanofi Genzyme and has received speaker honoraria and travel support from Amicus Therapeutics, Sanofi Genzyme and Takeda/Shire. JPO has received consulting honoraria and unrestricted research grants and funding for research projects from Sanofi Genzyme, has received speaker honoraria from Sanofi Genzyme and Takeda/Shire and has received conference and travel support from Amicus Therapeutics, Sanofi Genzyme and Takeda/Shire. DGB has received speaker honoraria from Amicus Therapeutics, Sanofi Genzyme and Takeda/Shire. HWY has received honoraria from Sanofi Genzyme. RJH has received consulting honoraria from Sanofi Genzyme, Amicus Therapeutics, Protalix Corporation and Takeda/Shire, was an investigator in clinical trials sponsored by Amicus Therapeutics, Sanofi Genzyme and Takeda/Shire and received research funding from Sanofi Genzyme, Protalix Corporation and Amicus Therapeutics; these activities have been monitored and found to be in compliance with the conflict of interest policies at Cincinnati Children’s Hospital Medical Center. RL is an employee of Sanofi Genzyme. JP has received honoraria and travel support from Amicus Therapeutics, Protalix Corporation, Sanofi Genzyme and Takeda/Shire. CW has received research support from Sanofi Genzyme and is a consultant for Actelion Pharmaceuticals, Protalix Corporation, Boehringer Ingelheim GmbH and Sanofi Genzyme. WRW consults for Sanofi Genzyme and was an investigator in clinical studies and trials sponsored by Amicus Therapeutics, Protalix Corporation, Sanofi Genzyme and Takeda/Shire and has received research funding from Sanofi Genzyme, Amicus Therapeutics and Takeda/Shire; these activities are monitored and are in compliance with the conflict of interest policies at Emory University School of Medicine. DGW received consulting honoraria from Amicus Therapeutics, Sanofi Genzyme, Actelion Pharmaceuticals, AVROBIO, Freeline Therapeutics and Protalix Biotherapeutics and has received research funding from Amicus Therapeutics and Sanofi Genzyme. DPG, JPO, DGB, HWY, RJH, JP and CW are Regional or International Fabry Registry Board members and have received Fabry Registry Board honoraria., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
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38. Role of CD47 in Hematological Malignancies.
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Eladl E, Tremblay-LeMay R, Rastgoo N, Musani R, Chen W, Liu A, and Chang H
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- Angiogenic Proteins metabolism, Animals, Antibodies, Monoclonal, Humanized therapeutic use, Antigens, Differentiation metabolism, Antineoplastic Agents, Immunological therapeutic use, CD47 Antigen antagonists & inhibitors, Clinical Trials as Topic, Drug Delivery Systems, Drug Design, Drug Screening Assays, Antitumor, Hematologic Neoplasms therapy, Humans, Integrins metabolism, Leukemia metabolism, Leukemia physiopathology, Lymphoma, Non-Hodgkin metabolism, Lymphoma, Non-Hodgkin physiopathology, Molecular Mimicry, Myeloid Cells metabolism, Neoplasm Metastasis, Neoplasm Proteins antagonists & inhibitors, Oligopeptides therapeutic use, Protein Binding, Protein Domains, Protein Interaction Mapping, Receptors, Immunologic antagonists & inhibitors, Receptors, Immunologic metabolism, Signal Transduction physiology, CD47 Antigen physiology, Hematologic Neoplasms physiopathology, Molecular Targeted Therapy, Neoplasm Proteins physiology
- Abstract
CD47, or integrin-associated protein, is a cell surface ligand expressed in low levels by nearly all cells of the body. It plays an integral role in various immune responses as well as autoimmunity, by sending a potent "don't eat me" signal to prevent phagocytosis. A growing body of evidence demonstrates that CD47 is overexpressed in various hematological malignancies and its interaction with SIRPα on the phagocytic cells prevents phagocytosis of cancer cells. Additionally, it is expressed by different cell types in the tumor microenvironment and is required for establishing tumor metastasis. Overexpression of CD47 is thus often associated with poor clinical outcomes. CD47 has emerged as a potential therapeutic target and is being investigated in various preclinical studies as well as clinical trials to prove its safety and efficacy in treating hematological neoplasms. This review focuses on different therapeutic mechanisms to target CD47, either alone or in combination with other cell surface markers, and its pivotal role in impairing tumor growth and metastatic spread of various types of hematological malignancies.
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- 2020
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39. EZH2 as a therapeutic target for multiple myeloma and other haematological malignancies.
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Tremblay-LeMay R, Rastgoo N, Pourabdollah M, and Chang H
- Abstract
Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is of great interest in human cancer. It has been shown to have a dual nature, as it can act as a gene repressor or activator. Studies have highlighted the various roles of EZH2 in the pathophysiology of multiple myeloma (MM). It was also shown to have a role in the development of drug resistance in MM. There are several ongoing clinical trials of EZH2 inhibitors in haematological malignancies. Pre-clinical studies have provided a rationale for the therapeutic relevance of EZH2 inhibitors in MM. This paper reviews the evidence supporting the role of EZH2 in MM pathophysiology and drug resistance, with an emphasis on interactions between EZH2 and microRNAs, as well as the prognostic significance of EZH2 expression in MM. Furthermore, results from the pre-clinical studies of EZH2 inhibition in MM and currently available interim results from clinical trials of EZH2 inhibitors in haematological malignancies are presented. Preliminary data exploring anticipated mechanisms of resistance to EZH2 inhibitors are also reviewed. There is therefore strong evidence to support the relevance of targeting EZH2 for the treatment of MM., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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- 2018
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40. Concurrent JAK2 mutation and isolated del(5q) associated with marrow fibrosis and small hypo/monolobated megakaryocytes.
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Tremblay-LeMay R and Chang H
- Subjects
- Aged, Female, Humans, Bone Marrow metabolism, Bone Marrow pathology, Chromosome Deletion, Chromosomes, Human, Pair 5 genetics, Chromosomes, Human, Pair 5 metabolism, Janus Kinase 2 genetics, Janus Kinase 2 metabolism, Megakaryocytes metabolism, Megakaryocytes pathology, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes metabolism, Myelodysplastic Syndromes pathology
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- 2018
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41. Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway.
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Tremblay-LeMay R, Rastgoo N, and Chang H
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- Humans, Multiple Myeloma drug therapy, Programmed Cell Death 1 Receptor metabolism
- Abstract
Even with recent advances in therapy regimen, multiple myeloma patients commonly develop drug resistance and relapse. The relevance of targeting the PD-1/PD-L1 axis has been demonstrated in pre-clinical models. Monotherapy with PD-1 inhibitors produced disappointing results, but combinations with other drugs used in the treatment of multiple myeloma seemed promising, and clinical trials are ongoing. However, there have recently been concerns about the safety of PD-1 and PD-L1 inhibitors combined with immunomodulators in the treatment of multiple myeloma, and several trials have been suspended. There is therefore a need for alternative combinations of drugs or different approaches to target this pathway. Protein expression of PD-L1 on cancer cells, including in multiple myeloma, has been associated with intrinsic aggressive features independent of immune evasion mechanisms, thereby providing a rationale for the adoption of new strategies directly targeting PD-L1 protein expression. Drugs modulating the transcriptional and post-transcriptional regulation of PD-L1 could represent new therapeutic strategies for the treatment of multiple myeloma, help potentiate the action of other drugs or be combined to PD-1/PD-L1 inhibitors in order to avoid the potentially problematic combination with immunomodulators. This review will focus on the pathophysiology of PD-L1 expression in multiple myeloma and drugs that have been shown to modulate this expression.
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- 2018
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42. Tumor Cell Invasion Induced by Radiation in Balb/C Mouse is Prevented by the Cox-2 Inhibitor NS-398.
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Lemay R, Lepage M, Tremblay L, Therriault H, Charest G, and Paquette B
- Subjects
- Animals, Cell Line, Tumor, Cell Movement radiation effects, Cyclooxygenase 2 Inhibitors pharmacology, Drug Screening Assays, Antitumor, Inflammation Mediators metabolism, Mammary Neoplasms, Experimental blood supply, Matrix Metalloproteinase 2 analysis, Mice, Mice, Inbred BALB C, Neoplasm Metastasis prevention & control, Neoplasm Proteins analysis, Neoplasm Transplantation, Nitrobenzenes pharmacology, Radiotherapy adverse effects, Sulfonamides pharmacology, Thigh, Transplantation, Heterotopic, Tumor Burden drug effects, Tumor Burden radiation effects, Gamma Rays adverse effects, Mammary Neoplasms, Experimental pathology, Neoplasm Invasiveness prevention & control, Nitrobenzenes therapeutic use, Sulfonamides therapeutic use
- Abstract
Radiation stimulates the expression of inflammatory mediators known to increase cancer cell invasion. Therefore, it is important to determine whether anti-inflammatory drugs can prevent this adverse effect of radiation. Since cyclooxygenase-2 (COX-2) is a central player in the inflammatory response, we performed studies to determine whether the COX-2 inhibitor NS-398 can reduce the radiation enhancement of cancer cell invasion. Thighs of Balb/c mice treated with NS-398 were irradiated with either daily fractions of 7.5 Gy for five consecutive days or a single 30 Gy dose prior to subcutaneous injection of nonirradiated MC7-L1 mammary cancer cells. Five weeks later, tumor invasion, blood vessel permeability and interstitial volumes were assessed using magnetic resonance imaging (MRI). Matrix metalloproteinase-2 (MMP-2) was measured in tissues by zymography at 21 days postirradiation. Cancer cell invasion in the mouse thighs was increased by 12-fold after fractionated irradiations (5 × 7.5 Gy) and by 17-fold after a single 30 Gy dose of radiation. This stimulation of cancer cell invasion was accompanied by a significant increase in the interstitial volume and a higher level of the protease MMP-2. NS-398 treatment largely prevented the stimulation of cancer cell invasion, which was associated with a reduction in interstitial volume in the irradiated thighs and a complete suppression of MMP-2 stimulation. In conclusion, this animal model using MC7-L1 cells demonstrates that radiation-induced cancer cell invasion can be largely prevented with the COX-2 inhibitor NS-398.
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- 2017
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43. How Wide Should Margins Be for Phyllodes Tumors of the Breast?
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Tremblay-LeMay R, Hogue JC, Provencher L, Poirier B, Poirier É, Laberge S, Diorio C, and Desbiens C
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- Adult, Aged, Biopsy, Fine-Needle statistics & numerical data, Breast Neoplasms diagnostic imaging, Breast Neoplasms epidemiology, Breast Neoplasms pathology, Female, Follow-Up Studies, Humans, Mastectomy statistics & numerical data, Middle Aged, Neoplasm Recurrence, Local pathology, Phyllodes Tumor diagnostic imaging, Phyllodes Tumor epidemiology, Phyllodes Tumor pathology, Quebec epidemiology, Breast Neoplasms surgery, Margins of Excision, Phyllodes Tumor surgery
- Abstract
The surgical management of phyllodes tumors (PTs) is still controversial. Some studies have suggested surgical margins ≥1 cm, but recent studies suggested that negative margins could be appropriate regardless of their width. To evaluate recurrence rates of PTs following surgery according to margins. Retrospective study of women who attended a tertiary breast cancer reference center between 1998 and 2010: 142 patients with a PT diagnosis, either at minimally invasive breast biopsy or at surgery, were identified. Clinical, pathologic and follow-up characteristics were assessed. Among 140 patients who underwent surgery, 64.3% of biopsies accurately predicted the final PT diagnosis at surgery. Forty-two (42/87, 48.3%) PTs had positive margins. Twenty-one (21/42, 50.0%) patients had a surgical revision of margins. Only one (1/42, 2.4%) had margins greater or equal to 1 cm. After a median follow-up of 1.29 years in benign PTs, 4.99 years in borderline PTs, and 5.42 years in malignant PTs, there were five local recurrences, three in originally benign PTs and two in borderline PTs. All were managed with surgery. Four had initial margins ≤1 mm. One patient with borderline PT had a local recurrence and later progressed to regional recurrence and metastasis. Free surgical margins are necessary to treat PT, and margins of at least 1 mm might be sufficient to prevent recurrence. Core needle biopsy might not be the best diagnostic tool for PTs., (© 2016 Wiley Periodicals, Inc.)
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- 2017
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44. Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy: Data from the Fabry Registry.
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Hopkin RJ, Cabrera G, Charrow J, Lemay R, Martins AM, Mauer M, Ortiz A, Patel MR, Sims K, Waldek S, Warnock DG, and Wilcox WR
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- Adult, Child, Enzyme Replacement Therapy adverse effects, Fabry Disease complications, Fabry Disease mortality, Fabry Disease physiopathology, Female, Humans, Isoenzymes adverse effects, Kidney Diseases complications, Kidney Diseases mortality, Kidney Diseases physiopathology, Kidney Transplantation, Male, Middle Aged, Registries, Risk Factors, Severity of Illness Index, Stroke complications, Stroke mortality, Stroke physiopathology, alpha-Galactosidase adverse effects, Fabry Disease drug therapy, Isoenzymes administration & dosage, Kidney Diseases drug therapy, Stroke drug therapy, alpha-Galactosidase administration & dosage
- Abstract
Background: Fabry disease, an X-linked lysosomal storage disorder, causes intracellular accumulation of glycosphingolipids leading to progressive renal, cardiovascular, and cerebrovascular disease, and premature death., Methods: This longitudinal Fabry Registry study analyzed data from patients with Fabry disease to determine the incidence and type of severe clinical events following initiation of enzyme replacement therapy (ERT) with agalsidase beta, as well as risk factors associated with occurrence of these events. Severe events assessed included chronic dialysis, renal transplantation, cardiac events, stroke, and death., Results: The analyses included 969 male and 442 female Fabry patients. The mean age at first agalsidase beta infusion was 35 and 44, and median treatment follow-up 4.3years and 3.2years, respectively. Among males, cardiac events were the most common on-ERT events, followed by renal, stroke, and non-cardiac death. Among females, cardiac events were also most common followed by stroke and renal events. Patients with on-ERT events had significantly more advanced cardiac and renal disease at baseline as compared with patients without on-ERT events. Severe events were also associated with older age at ERT initiation (males and females), a history of pre-ERT events (females; approaching statistical significance in males), and a higher urinary protein/creatinine ratio (females). Approximately 65% of patients with pre-ERT events did not experience subsequent on-ERT events. Of patients without pre-ERT events, most (84% of males, 92% of females) remained event-free., Conclusions: Patients with on-ERT severe events had more advanced Fabry organ involvement at baseline than those without such events and patients who initiated ERT at a younger age had less residual risk of on-ERT events. The observed patterns of residual risk may aid clinicians in multidisciplinary monitoring of male and female patients with Fabry disease receiving ERT, and in determining the need for administration of adjunctive therapies., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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45. Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease.
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Germain DP, Charrow J, Desnick RJ, Guffon N, Kempf J, Lachmann RH, Lemay R, Linthorst GE, Packman S, Scott CR, Waldek S, Warnock DG, Weinreb NJ, and Wilcox WR
- Subjects
- Adolescent, Adult, Fabry Disease complications, Fabry Disease genetics, Female, Follow-Up Studies, Humans, Kidney Diseases diagnosis, Kidney Diseases etiology, Kidney Diseases physiopathology, Male, Middle Aged, Recombinant Proteins therapeutic use, Treatment Outcome, Young Adult, Enzyme Replacement Therapy, Fabry Disease drug therapy, Isoenzymes therapeutic use, alpha-Galactosidase therapeutic use
- Abstract
Background: Fabry disease results from deficient α-galactosidase A activity and globotriaosylceramide accumulation causing renal insufficiency, strokes, hypertrophic cardiomyopathy and early demise. We assessed the 10-year outcome of recombinant α-galactosidase A therapy., Methods: The outcomes (severe clinical events, renal function, cardiac structure) of 52/58 patients with classic Fabry disease from the phase 3 clinical trial and extension study, and the Fabry Registry were evaluated. Disease progression rates for patients with low renal involvement (LRI, n=32) or high renal involvement (HRI, n=20) at baseline were assessed., Results: 81% of patients (42/52) did not experience any severe clinical event during the treatment interval and 94% (49/52) were alive at the end of the study period. Ten patients reported a total of 16 events. Patients classified as LRI started therapy 13 years younger than HRI (mean 25 years vs 38 years). Mean slopes for estimated glomerular filtration rate for LRI and HRI were -1.89 mL/min/1.73 m(2)/year and -6.82 mL/min/1.73 m(2)/year, respectively. Overall, the mean left ventricular posterior wall thickness and interventricular septum thickness remained unchanged and normal. Patients who initiated treatment at age ≥ 40 years exhibited significant increase in left ventricular posterior wall thickness and interventricular septum thickness. Mean plasma globotriaosylceramide normalised within 6 months., Conclusions: This 10-year study documents the effectiveness of agalsidase beta (1 mg/kg/2 weeks) in patients with Fabry disease. Most patients remained alive and event-free. Patients who initiated treatment at a younger age and with less kidney involvement benefited the most from therapy. Patients who initiated treatment at older ages and/or had advanced renal disease experienced disease progression., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
- Published
- 2015
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46. Alcohol and HER2 polymorphisms as risk factor for cardiotoxicity in breast cancer treated with trastuzumab.
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Lemieux J, Diorio C, Côté MA, Provencher L, Barabé F, Jacob S, St-Pierre C, Demers E, Tremblay-Lemay R, Nadeau-Larochelle C, Michaud A, and Laflamme C
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Agents therapeutic use, Breast Neoplasms genetics, Cohort Studies, Female, Genotype, Heart drug effects, Heart Failure chemically induced, Humans, Middle Aged, Polymorphism, Single Nucleotide, Receptor, ErbB-2 genetics, Receptor, ErbB-2 metabolism, Retrospective Studies, Risk Factors, Surveys and Questionnaires, Trastuzumab, Ventricular Function, Left drug effects, Alcohol Drinking, Antibodies, Monoclonal, Humanized adverse effects, Antineoplastic Agents adverse effects, Breast Neoplasms drug therapy, Cardiotoxins, Genes, erbB-2, Heart Diseases chemically induced
- Abstract
Background: Trastuzumab has no major side-effects except the potential for cardiac toxicity. The main objective of this study was to evaluate the association between trastuzumab-associated cardiac toxicity and two potential risk factors: alcohol intake and HER2 polymorphisms., Patients and Methods: In a retrospective cohort study of 237 women with non-metastatic HER2-positive breast cancer treated with trastuzumab, traditional risk factors were assessed by review of medical records, alcohol use by an administered questionnaire to women (n=132), and HER2 polymorphisms (Ile655Val and Ala1170Pro) using TaqMan assays (n=73)., Results: Association was observed between alcohol intake (10 drinks and more per week) during the trastuzumab treatment and cardiac toxicity (p=0.04). For polymorphisms, compared to Ile/Ile carriers, HER2 Ile/Val was associated with a higher risk of cardiac toxicity (p=0.02)., Conclusion: Heavy alcohol use during the course of trastuzumab treatment and the HER2 Ile/Val genotype may constitute risk factors for cardiac toxicity.
- Published
- 2013
47. Cancer radiotherapy based on femtosecond IR laser-beam filamentation yielding ultra-high dose rates and zero entrance dose.
- Author
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Meesat R, Belmouaddine H, Allard JF, Tanguay-Renaud C, Lemay R, Brastaviceanu T, Tremblay L, Paquette B, Wagner JR, Jay-Gerin JP, Lepage M, Huels MA, and Houde D
- Subjects
- Animals, Biophysics methods, Cell Line, Tumor, DNA Damage, Equipment Design, Female, Heavy Ion Radiotherapy, Humans, Laser Therapy methods, Mice, Mice, Inbred BALB C, Radiation Oncology methods, Radiometry methods, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted methods, Thymidine chemistry, Infrared Rays, Neoplasms drug therapy, Neoplasms radiotherapy
- Abstract
Since the invention of cancer radiotherapy, its primary goal has been to maximize lethal radiation doses to the tumor volume while keeping the dose to surrounding healthy tissues at zero. Sadly, conventional radiation sources (γ or X rays, electrons) used for decades, including multiple or modulated beams, inevitably deposit the majority of their dose in front or behind the tumor, thus damaging healthy tissue and causing secondary cancers years after treatment. Even the most recent pioneering advances in costly proton or carbon ion therapies can not completely avoid dose buildup in front of the tumor volume. Here we show that this ultimate goal of radiotherapy is yet within our reach: Using intense ultra-short infrared laser pulses we can now deposit a very large energy dose at unprecedented microscopic dose rates (up to 10(11) Gy/s) deep inside an adjustable, well-controlled macroscopic volume, without any dose deposit in front or behind the target volume. Our infrared laser pulses produce high density avalanches of low energy electrons via laser filamentation, a phenomenon that results in a spatial energy density and temporal dose rate that both exceed by orders of magnitude any values previously reported even for the most intense clinical radiotherapy systems. Moreover, we show that (i) the type of final damage and its mechanisms in aqueous media, at the molecular and biomolecular level, is comparable to that of conventional ionizing radiation, and (ii) at the tumor tissue level in an animal cancer model, the laser irradiation method shows clear therapeutic benefits.
- Published
- 2012
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48. Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation.
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Warnock DG, Ortiz A, Mauer M, Linthorst GE, Oliveira JP, Serra AL, Maródi L, Mignani R, Vujkovac B, Beitner-Johnson D, Lemay R, Cole JA, Svarstad E, Waldek S, Germain DP, and Wanner C
- Subjects
- Adult, Creatinine urine, Disease Progression, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic diagnosis, Kidney Function Tests, Male, Middle Aged, Prognosis, Proteinuria diagnosis, Time Factors, Enzyme Replacement Therapy, Fabry Disease complications, Fabry Disease therapy, Isoenzymes therapeutic use, Kidney Failure, Chronic etiology, Proteinuria etiology, alpha-Galactosidase therapeutic use
- Abstract
Background: The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta., Methods: Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment. Multivariate logistic regression analyses were used to identify factors associated with renal disease progression., Results: Men within the first quartile had a mean eGFR slope of -0.1 mL/min/1.73m(2)/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of -6.7 mL/min/1.73m(2)/year. The risk factor most strongly associated with renal disease progression was averaged urinary protein:creatinine ratio (UP/Cr) ≥1 g/g (odds ratio 112, 95% confidence interval (95% CI) 4-3109, P = 0.0054). Longer time from symptom onset to treatment was also associated with renal disease progression (odds ratio 19, 95% CI 2-184, P = 0.0098). Women in Quartile 4 had the highest averaged UP/Cr (mean 1.8 g/g) and the most rapid renal disease progression: (mean slope -4.4 mL/min/1.73m(2)/year)., Conclusions: Adults with Fabry disease are at risk for progressive loss of eGFR despite enzyme replacement therapy, particularly if proteinuria is ≥1 g/g. Men with little urinary protein excretion and those who began receiving agalsidase beta sooner after the onset of symptoms had stable renal function. These findings suggest that early intervention may lead to optimal renal outcomes.
- Published
- 2012
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49. Irradiation of normal mouse tissue increases the invasiveness of mammary cancer cells.
- Author
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Lemay R, Archambault M, Tremblay L, Bujold R, Lepage M, and Paquette B
- Subjects
- Animals, Cell Line, Tumor, Cell Proliferation, Female, Magnetic Resonance Imaging methods, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 9 metabolism, Mice, Mice, Inbred BALB C, Neoplasm Transplantation, Radiotherapy methods, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Mammary Neoplasms, Animal metabolism, Mammary Neoplasms, Animal radiotherapy, Neoplasm Invasiveness
- Abstract
Purpose: Treatment of breast tumours frequently involves irradiating the whole breast to reach malignant microfoci scattered throughout the breast. In this study, we determined whether irradiation of normal tissues could increase the invasiveness of breast cancer cells in a mouse model., Materials and Methods: Non-irradiated MC7-L1 mouse mammary carcinoma cells were injected subcutaneously in irradiated and non-irradiated thighs of Balb/c mice. The invasion volume, tumour volume, blood vessel permeability and interstitial volumes were monitored by magnetic resonance imaging (MRI). Slices of normal tissue invaded by cancer cells were examined by histology. Activity of matrix metalloproteinase -2 and -9 (MMP -2 and -9) in healthy and irradiated tissues was determined, and the proliferation index of the invading cancer cells was evaluated., Results: Three weeks after irradiation, enhancement of MC7-L1 cells invasiveness in irradiated thighs was already detected by MRI. The tumour invasion volume continued to extend 28- to 37-fold compared to the non-irradiated implantation site for the following three weeks, and it was associated with an increase of MMP-2 and -9 activities in healthy tissues. The interstitial volume associated with invading cancer cells was significantly larger in the pre-irradiated sites; while the blood vessels permeability was not altered. Cancer cells invading the healthy tissues were proliferating at a lower rate compared to non-invading cancer cells., Conclusion: Implantation of non-irradiated mammary cancer cells in previously irradiated normal tissue enhances the invasive capacity of the mammary cancer cells and is associated with an increased activity of MMP-2 and -9 in the irradiated normal tissue.
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- 2011
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50. Prognostic indicators of renal disease progression in adults with Fabry disease: natural history data from the Fabry Registry.
- Author
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Wanner C, Oliveira JP, Ortiz A, Mauer M, Germain DP, Linthorst GE, Serra AL, Maródi L, Mignani R, Cianciaruso B, Vujkovac B, Lemay R, Beitner-Johnson D, Waldek S, and Warnock DG
- Subjects
- Adult, Creatinine urine, Disease Progression, Enzyme Replacement Therapy, Fabry Disease therapy, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic etiology, Male, Middle Aged, Prognosis, Proteinuria complications, Registries, Fabry Disease complications, Kidney Diseases etiology
- Abstract
Background and Objectives: These analyses were designed to characterize renal disease progression in untreated adults with Fabry disease., Design, Setting, Participants, & Measurements: Data from the Fabry Registry for 462 untreated adults (121 men and 341 women) who had at least two estimated GFR (eGFR) values over a span of ≥12 months before starting enzyme replacement therapy were included., Results: Most men (86 of 121, 71%) had more rapid loss of kidney function than the normal adult population (loss of eGFR > -1 ml/min per 1.73 m(2) per year), whereas fewer women (133 of 341, 39%) had rapid loss of kidney function. Patients with rapid progression had significantly higher mean averaged urinary protein to urinary creatinine ratios (UP/Cr) than patients with slower progression (1.5 versus 0.2 for men; 1.4 versus 0.5 for women; P < 0.0001). Patients were grouped into quartiles based on averaged UP/Cr; renal function in men declined more rapidly with higher UP/Cr, with the steepest declines observed in men with UP/Cr > 1.5 (mean eGFR slope, -5.6 ml/min per 1.73 m(2) per year; n = 30). eGFR slope declined more slowly in women, with the steepest declines observed in women with UP/Cr > 1.2 (mean eGFR slope, -1.3 ml/min per 1.73 m(2) per year; n = 85). Regression models of eGFR slope indicated that UP/Cr is the most important indicator of renal disease progression in adult Fabry patients. In women, lower baseline eGFR and age were also associated with renal disease progression. Women who had clinical events had more rapid loss of kidney function., Conclusions: Urinary protein excretion is strongly associated with renal disease progression in men and women with Fabry disease.
- Published
- 2010
- Full Text
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