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4 results on '"Fleming, Adam J."'

1. Leptin is Associated with the Tri-Ponderal Mass Index in Children: A Cross-Sectional Study

Author

Empringham,Brianna, Jennings,William J, Rajan,Raeesha, Fleming,Adam J, Portwine,Carol, Johnston,Donna L, Zelcer,Shayna M, Rassekh,Shahrad Rod, Tran,Victoria, Burrow,Sarah, Thabane,Lehana, Samaan,M Constantine, Empringham,Brianna, Jennings,William J, Rajan,Raeesha, Fleming,Adam J, Portwine,Carol, Johnston,Donna L, Zelcer,Shayna M, Rassekh,Shahrad Rod, Tran,Victoria, Burrow,Sarah, Thabane,Lehana, and Samaan,M Constantine

Abstract

Brianna Empringham,1,2 William J Jennings,1,2 Raeesha Rajan,1– 3 Adam J Fleming,1,4 Carol Portwine,1,4 Donna L Johnston,5 Shayna M Zelcer,6 Shahrad Rod Rassekh,7 Victoria Tran,1,2 Sarah Burrow,8 Lehana Thabane,3,9– 11 M Constantine Samaan1– 3 1Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; 2Division of Pediatric Endocrinology, McMaster Children’s Hospital, Hamilton, Ontario, Canada; 3Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada; 4Division of Pediatric Hematology/Oncology, McMaster Children’s Hospital, Hamilton, Ontario, Canada; 5Division of Pediatric Hematology/Oncology, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada; 6Pediatric Hematology Oncology, Children’s Hospital, London Health Sciences Center, London, Ontario, Canada; 7Division of Pediatric Hematology/Oncology/BMT, Department of Pediatrics, British Columbia’s Children’s Hospital, Vancouver, BC, Canada; 8Division of Orthopedic Surgery, Department of Surgery, McMaster University Medical Centre, Hamilton, Ontario, Canada; 9Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada; 10Centre for Evaluation of Medicines, St. Joseph’s Health Care, Hamilton, Ontario, Canada; 11Biostatistics Unit, St Joseph’s Healthcare-Hamilton, Hamilton, Ontario, CanadaCorrespondence: M Constantine SamaanDepartment of Pediatrics, McMaster University, Division of Pediatric Endocrinology, McMaster Children’s Hospital, 1280 Main Street West, 3A-57, Hamilton, Ontario, L8S 4K1 Tel +001-905-521-2100, ext. 75926Fax +001-905-308-7548Email samaanc@mcmaster.caBackground: Obesity is characterized by the disproportionate expansion of the fat mass and is most commonly diagnosed using the Body Mass Index (BMI) z-score or percentile in children. However, these measures associate poorly with the fat mass. This i

Published
2021

2. Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors.

Author

Torchia, Jonathon, Torchia, Jonathon, Golbourn, Brian, Feng, Shengrui, Ho, King Ching, Sin-Chan, Patrick, Vasiljevic, Alexandre, Norman, Joseph D, Guilhamon, Paul, Garzia, Livia, Agamez, Natalia R, Lu, Mei, Chan, Tiffany S, Picard, Daniel, de Antonellis, Pasqualino, Khuong-Quang, Dong-Anh, Planello, Aline C, Zeller, Constanze, Barsyte-Lovejoy, Dalia, Lafay-Cousin, Lucie, Letourneau, Louis, Bourgey, Mathieu, Yu, Man, Gendoo, Deena MA, Dzamba, Misko, Barszczyk, Mark, Medina, Tiago, Riemenschneider, Alexandra N, Morrissy, A Sorana, Ra, Young-Shin, Ramaswamy, Vijay, Remke, Marc, Dunham, Christopher P, Yip, Stephen, Ng, Ho-Keung, Lu, Jian-Qiang, Mehta, Vivek, Albrecht, Steffen, Pimentel, Jose, Chan, Jennifer A, Somers, Gino R, Faria, Claudia C, Roque, Lucia, Fouladi, Maryam, Hoffman, Lindsey M, Moore, Andrew S, Wang, Yin, Choi, Seung Ah, Hansford, Jordan R, Catchpoole, Daniel, Birks, Diane K, Foreman, Nicholas K, Strother, Doug, Klekner, Almos, Bognár, Laszló, Garami, Miklós, Hauser, Péter, Hortobágyi, Tibor, Wilson, Beverly, Hukin, Juliette, Carret, Anne-Sophie, Van Meter, Timothy E, Hwang, Eugene I, Gajjar, Amar, Chiou, Shih-Hwa, Nakamura, Hideo, Toledano, Helen, Fried, Iris, Fults, Daniel, Wataya, Takafumi, Fryer, Chris, Eisenstat, David D, Scheinemann, Katrin, Fleming, Adam J, Johnston, Donna L, Michaud, Jean, Zelcer, Shayna, Hammond, Robert, Afzal, Samina, Ramsay, David A, Sirachainan, Nongnuch, Hongeng, Suradej, Larbcharoensub, Noppadol, Grundy, Richard G, Lulla, Rishi R, Fangusaro, Jason R, Druker, Harriet, Bartels, Ute, Grant, Ronald, Malkin, David, McGlade, C Jane, Nicolaides, Theodore, Tihan, Tarik, Phillips, Joanna, Majewski, Jacek, Montpetit, Alexandre, Bourque, Guillaume, Bader, Gary D, Reddy, Alyssa T, Gillespie, G Yancey, Warmuth-Metz, Monika, Torchia, Jonathon, Torchia, Jonathon, Golbourn, Brian, Feng, Shengrui, Ho, King Ching, Sin-Chan, Patrick, Vasiljevic, Alexandre, Norman, Joseph D, Guilhamon, Paul, Garzia, Livia, Agamez, Natalia R, Lu, Mei, Chan, Tiffany S, Picard, Daniel, de Antonellis, Pasqualino, Khuong-Quang, Dong-Anh, Planello, Aline C, Zeller, Constanze, Barsyte-Lovejoy, Dalia, Lafay-Cousin, Lucie, Letourneau, Louis, Bourgey, Mathieu, Yu, Man, Gendoo, Deena MA, Dzamba, Misko, Barszczyk, Mark, Medina, Tiago, Riemenschneider, Alexandra N, Morrissy, A Sorana, Ra, Young-Shin, Ramaswamy, Vijay, Remke, Marc, Dunham, Christopher P, Yip, Stephen, Ng, Ho-Keung, Lu, Jian-Qiang, Mehta, Vivek, Albrecht, Steffen, Pimentel, Jose, Chan, Jennifer A, Somers, Gino R, Faria, Claudia C, Roque, Lucia, Fouladi, Maryam, Hoffman, Lindsey M, Moore, Andrew S, Wang, Yin, Choi, Seung Ah, Hansford, Jordan R, Catchpoole, Daniel, Birks, Diane K, Foreman, Nicholas K, Strother, Doug, Klekner, Almos, Bognár, Laszló, Garami, Miklós, Hauser, Péter, Hortobágyi, Tibor, Wilson, Beverly, Hukin, Juliette, Carret, Anne-Sophie, Van Meter, Timothy E, Hwang, Eugene I, Gajjar, Amar, Chiou, Shih-Hwa, Nakamura, Hideo, Toledano, Helen, Fried, Iris, Fults, Daniel, Wataya, Takafumi, Fryer, Chris, Eisenstat, David D, Scheinemann, Katrin, Fleming, Adam J, Johnston, Donna L, Michaud, Jean, Zelcer, Shayna, Hammond, Robert, Afzal, Samina, Ramsay, David A, Sirachainan, Nongnuch, Hongeng, Suradej, Larbcharoensub, Noppadol, Grundy, Richard G, Lulla, Rishi R, Fangusaro, Jason R, Druker, Harriet, Bartels, Ute, Grant, Ronald, Malkin, David, McGlade, C Jane, Nicolaides, Theodore, Tihan, Tarik, Phillips, Joanna, Majewski, Jacek, Montpetit, Alexandre, Bourque, Guillaume, Bader, Gary D, Reddy, Alyssa T, Gillespie, G Yancey, and Warmuth-Metz, Monika

Abstract

We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.

Published
2016

3. Molecular subgroups of atypical teratoid rhabdoid tumours in children : an integrated genomic and clinicopathological analysis

Author

Torchia, Jonathon, Picard, Daniel, Lafay-Cousin, Lucie, Hawkins, Cynthia E., Kim, Seung-Ki, Letourneau, Louis, Ra, Young-Shin, Ho, King Ching, Chan, Tiffany Sin Yu, Sin-Chan, Patrick, Dunham, Christopher P., Yip, Stephen, Ng, Ho-Keung, Lu, Jian-Qiang, Albrecht, Steffen, Pimentel, Jose, Chan, Jennifer A., Somers, Gino R., Zielenska, Maria, Faria, Claudia C., Roque, Lucia, Baskin, Berivan, Birks, Diane, Foreman, Nick, Strother, Douglas, Klekner, Almos, Garami, Miklos, Hauser, Peter, Hortobagyi, Tibor, Bognar, Laszlo, Wilson, Beverly, Hukin, Juliette, Carret, Anne-Sophie, Van Meter, Timothy E., Nakamura, Hideo, Toledano, Helen, Fried, Iris, Fults, Daniel, Wataya, Takafumi, Fryer, Chris, Eisenstat, David D., Scheineman, Katrin, Johnston, Donna, Michaud, Jean, Zelcer, Shayna, Hammond, Robert, Ramsay, David A., Fleming, Adam J., Lulla, Rishi R., Fangusaro, Jason R., Sirachainan, Nongnuch, Larbcharoensub, Noppadol, Hongeng, Suradej, Barakzai, Muhammad Abrar, Montpetit, Alexandre, Stephens, Derek, Grundy, Richard G., Schueller, Ulrich, Nicolaides, Theodore, Tihan, Tarik, Phillips, Joanna, Taylor, Michael D., Rutka, James T., Dirks, Peter, Bader, Gary D., Warmuth-Metz, Monika, Rutkowski, Stefan, Pietsch, Torsten, Judkins, Alexander R., Jabado, Nada, Bouffet, Eric, Huang, Annie, Torchia, Jonathon, Picard, Daniel, Lafay-Cousin, Lucie, Hawkins, Cynthia E., Kim, Seung-Ki, Letourneau, Louis, Ra, Young-Shin, Ho, King Ching, Chan, Tiffany Sin Yu, Sin-Chan, Patrick, Dunham, Christopher P., Yip, Stephen, Ng, Ho-Keung, Lu, Jian-Qiang, Albrecht, Steffen, Pimentel, Jose, Chan, Jennifer A., Somers, Gino R., Zielenska, Maria, Faria, Claudia C., Roque, Lucia, Baskin, Berivan, Birks, Diane, Foreman, Nick, Strother, Douglas, Klekner, Almos, Garami, Miklos, Hauser, Peter, Hortobagyi, Tibor, Bognar, Laszlo, Wilson, Beverly, Hukin, Juliette, Carret, Anne-Sophie, Van Meter, Timothy E., Nakamura, Hideo, Toledano, Helen, Fried, Iris, Fults, Daniel, Wataya, Takafumi, Fryer, Chris, Eisenstat, David D., Scheineman, Katrin, Johnston, Donna, Michaud, Jean, Zelcer, Shayna, Hammond, Robert, Ramsay, David A., Fleming, Adam J., Lulla, Rishi R., Fangusaro, Jason R., Sirachainan, Nongnuch, Larbcharoensub, Noppadol, Hongeng, Suradej, Barakzai, Muhammad Abrar, Montpetit, Alexandre, Stephens, Derek, Grundy, Richard G., Schueller, Ulrich, Nicolaides, Theodore, Tihan, Tarik, Phillips, Joanna, Taylor, Michael D., Rutka, James T., Dirks, Peter, Bader, Gary D., Warmuth-Metz, Monika, Rutkowski, Stefan, Pietsch, Torsten, Judkins, Alexander R., Jabado, Nada, Bouffet, Eric, and Huang, Annie

Abstract

Background Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. Methods We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. Findings Transcriptional analyses identified two atypical teratoid rhabdoid tumour subgroups with differential enrichment of genetic pathways, and distinct clinicopathological and survival features. Expression of ASCL1, a regulator of NOTCH signalling, correlated with supratentorial location (p=0.004) and superior 5-year overall survival (35%, 95% CI 13-57, and 20%, 6-34, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.033) in 70 patients who received multimodal treatment. ASCL1 expression also correlated with superior 5-year overall survival (34%, 7-61, and 9%, 0-21, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.001) in 39 patients who received only chemotherapy without radiation. Cox hazard ratios for overall survival in patients with differential ASCL1 enrichment treated with chemotherapy with or without radiation were 2.02 (95% CI 1.04-3.85; p=0.038) and 3.98 (1.71-9.26; p=0.001). Integrated analyses of molecular subgroupings with clinical prognostic factor

Published
2015
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4. Identification of nonferritin mitochondrial iron deposits in a mouse model of friedreich ataxia

Author

National Health and Medical Research Council (Australia), Muscular Dystrophy Association (US), Canadian Institutes of Health Research, Whitnall, Megan, Suryo Rahmanto, Yohan, Huang, Michael L. H., Saletta, Federica, Chuen Lok, Hiu, Gutiérrez, Lucía, Lázaro, Francisco J., Fleming, Adam J., Pierre, Timothy G. St., Mikhael, Marc R., Ponka, Prem, Richardson, Des R., National Health and Medical Research Council (Australia), Muscular Dystrophy Association (US), Canadian Institutes of Health Research, Whitnall, Megan, Suryo Rahmanto, Yohan, Huang, Michael L. H., Saletta, Federica, Chuen Lok, Hiu, Gutiérrez, Lucía, Lázaro, Francisco J., Fleming, Adam J., Pierre, Timothy G. St., Mikhael, Marc R., Ponka, Prem, and Richardson, Des R.

Abstract

There is no effective treatment for the cardiomyopathy of the most common autosomal recessive ataxia, Friedreich ataxia (FA). This disease is due to decreased expression of the mitochondrial protein, frataxin, which leads to alterations in mitochondrial iron (Fe) metabolism. The identification of potentially toxic mitochondrial Fe deposits in FA suggests Fe plays a role in its pathogenesis. Studies using the muscle creatine kinase (MCK) conditional frataxin knockout mouse that mirrors the disease have demonstrated frataxin deletion alters cardiac Fe metabolism. Indeed, there are pronounced changes in Fe trafficking away from the cytosol to the mitochondrion, leading to a cytosolic Fe deficiency. Considering Fe deficiency can induce apoptosis and cell death, we examined the effect of dietary Fe supplementation, which led to body Fe loading and limited the cardiac hypertrophy in MCK mutants. Furthermore, this study indicates a unique effect of heart and skeletal muscle-specific frataxin deletion on systemic Fe metabolism. Namely, frataxin deletion induces a signaling mechanism to increase systemic Fe levels and Fe loading in tissues where frataxin expression is intact (i.e., liver, kidney, and spleen). Examining the mutant heart, native size-exclusion chromatography, transmission electron microscopy, Mössbauer spectroscopy, and magnetic susceptibility measurements demonstrated that in the absence of frataxin, mitochondria contained biomineral Fe aggregates, which were distinctly different from isolated mammalian ferritin molecules. These mitochondrial aggregates of Fe, phosphorus, and sulfur, probably contribute to the oxidative stress and pathology observed in the absence of frataxin.

Published
2012

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