Search

Your search keyword '"Kauffman M"' showing total 556 results
Start Over Author "Kauffman M"
556 results on '"Kauffman M"'

5. KPT-330 has antitumour activity against non-small cell lung cancer

Author

Sun, H, Hattori, N, Chien, W, Sun, Q, Sudo, M, E-Ling, GL, Ding, L, Lim, SL, Shacham, S, Kauffman, M, Nakamaki, T, and Koeffler, HP

Subjects
Lung Cancer, Genetics, Cancer, Lung, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Animals, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Apoptosis, Carcinoma, Non-Small-Cell Lung, Cell Growth Processes, Cell Line, Tumor, Cisplatin, G1 Phase, Genes, p53, Humans, Hydrazines, Karyopherins, Lung Neoplasms, Male, Mice, Mice, Inbred NOD, Mice, SCID, Mutation, Receptors, Cytoplasmic and Nuclear, Triazoles, Xenograft Model Antitumor Assays, CRM1, SINE, NSCLC, p53, p73, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis
Abstract

BackgroundWe investigated the biologic and pharmacologic activities of a chromosome region maintenance 1 (CRM1) inhibitor against human non-small cell lung cancer (NSCLC) cells both in vitro and in vivo.MethodsThe in vitro and in vivo effects of a novel CRM1 inhibitor (KPT-330) for a large number of anticancer parameters were evaluated using a large panel of 11 NSCLC cell lines containing different key driver mutations. Mice bearing human NSCLC xenografts were treated with KPT-330, and tumour growth was assessed.ResultsKPT-330 inhibited proliferation and induced cell cycle arrest and apoptosis-related proteins in 11 NSCLC cells lines. Moreover, the combination of KPT-330 with cisplatin synergistically enhanced the cell kill of the NSCLC cells in vitro. Human NSCLC tumours growing in immunodeficient mice were markedly inhibited by KPT-330. Also, KPT-330 was effective even against NSCLC cells with a transforming mutation of either exon 20 of EGFR, TP53, phosphatase and tensin homologue, RAS or PIK3CA, suggesting the drug might be effective against a variety of lung cancers irrespective of their driver mutation.ConclusionsOur results support clinical testing of KPT-330 as a novel therapeutic strategy for NSCLC.

Published
2014

7. Behavioral responses of terrestrial mammals to COVID-19 lockdowns

Author

Tucker, M., Schipper, A., Adams, T., Attias, N., Avgar, T., Babic, N., Barker, K., Bastille-Rousseau, G., Behr, D., Belant, J., Beyer Jr, D., Blaum, N., Blount, D., Bockmühl, D., Pires Boulhosa, R. L., Brown, M., Buuveibaatar, B., Cagnacci, F., (0000-0003-0575-6408) Calabrese, J., Černe, R., Chamaillé-Jammes, S., Chan, A. N., Chase, M., Chaval, Y., Chenaux-Ibrahim, Y., Cherry, S., Ćirović, D., Çoban, E., Cole, E., Conlee, L., Courtemanch, A., Cozzi, G., Davidson, S., Debloois, D., Dejid, N., Denicola, V., Desbiez, A., Douglas-Hamilton, I., Drake, D., Egan, M., Eikelboom, J., Fagan, W., Farmer, M., Fennessy, J., Finnegan, S., Fleming, C., Fournier, B., Fowler, N., Gantchoff, M., Garnier, A., Gehr, B., Geremia, C., Goheen, J., Hauptfleisch, M., Hebblewhite, M., Heim, M., Hertel, A., Heurich, M., Hewison, M., Hodson, J., Hoffman, N., Hopcraft, G., Huber, D., Isaac, E., Janik, K., Ježek, M., Johansson, Ö., Jordan, N., Kaczensky, P., Kamaru, D., Kauffman, M., Kautz, T., Kays, R., Kelly, A., Kindberg, J., Krofel, M., Kusak, J., Lamb, C., Lasharr, T., Leimgruber, P., Leitner, H., Lierz, M., Linnell, J., Lkhagvaja, P., Long, R., López-Bao, J., Loretto, M.-C., Marchand, P., Martin, H., Martinez, L., Mcbride Jr, R., Mclaren, A., Meisingset, E., Melzheimer, J., Merrill, E., Middleton, A., Monteith, K., Moore, S., Moorter, B. V., Morellet, N., Morrison, T., Müller, R., Mysterud, A., Noonan, M., O’Connor, D., Olson, D., Olson, K., Ortega, A., Ossi, F., Panzacchi, M., Patchett, R., Patterson, B., Paula, R. C. D., Payne, J., Peters, W., Petroelje, T., Pitcher, B., Pokorny, B., Poole, K., Potočnik, H., Poulin, M.-P., Pringle, R., Prins, H., Ranc, N., Reljić, S., Robb, B., Röder, R., Rolandsen, C., Rutz, C., Salemgareyev, A., Samelius, G., Sayine-Crawford, H., Schooler, S., Şekercioğlu, Ç., Selva, N., Semenzato, P., Sergiel, A., Sharma, K., Shawler, A., Signer, J., Silovský, V., Silva, J., Simon, R., Smiley, R., Smith, D., Solberg, E., Soto, D., Spiegel, O., Stabach, J., Stacy-Dawes, J., Stahler, D., Stephenson, J., Stewart, C., Strand, O., Sunde, P., Svoboda, N., Swart, J., Thompson, J., Toal, K., Uiseb, K., Vanacker, M., Velilla, M., Verzuh, T., Wachter, B., Wagler, B., Whittington, J., Wikelski, M., Wilmers, C., Wittemyer, G., Young, J., Zięba, F., Zwijacz-Kozica, T., Huijbregts, M., Mueller, T., Tucker, M., Schipper, A., Adams, T., Attias, N., Avgar, T., Babic, N., Barker, K., Bastille-Rousseau, G., Behr, D., Belant, J., Beyer Jr, D., Blaum, N., Blount, D., Bockmühl, D., Pires Boulhosa, R. L., Brown, M., Buuveibaatar, B., Cagnacci, F., (0000-0003-0575-6408) Calabrese, J., Černe, R., Chamaillé-Jammes, S., Chan, A. N., Chase, M., Chaval, Y., Chenaux-Ibrahim, Y., Cherry, S., Ćirović, D., Çoban, E., Cole, E., Conlee, L., Courtemanch, A., Cozzi, G., Davidson, S., Debloois, D., Dejid, N., Denicola, V., Desbiez, A., Douglas-Hamilton, I., Drake, D., Egan, M., Eikelboom, J., Fagan, W., Farmer, M., Fennessy, J., Finnegan, S., Fleming, C., Fournier, B., Fowler, N., Gantchoff, M., Garnier, A., Gehr, B., Geremia, C., Goheen, J., Hauptfleisch, M., Hebblewhite, M., Heim, M., Hertel, A., Heurich, M., Hewison, M., Hodson, J., Hoffman, N., Hopcraft, G., Huber, D., Isaac, E., Janik, K., Ježek, M., Johansson, Ö., Jordan, N., Kaczensky, P., Kamaru, D., Kauffman, M., Kautz, T., Kays, R., Kelly, A., Kindberg, J., Krofel, M., Kusak, J., Lamb, C., Lasharr, T., Leimgruber, P., Leitner, H., Lierz, M., Linnell, J., Lkhagvaja, P., Long, R., López-Bao, J., Loretto, M.-C., Marchand, P., Martin, H., Martinez, L., Mcbride Jr, R., Mclaren, A., Meisingset, E., Melzheimer, J., Merrill, E., Middleton, A., Monteith, K., Moore, S., Moorter, B. V., Morellet, N., Morrison, T., Müller, R., Mysterud, A., Noonan, M., O’Connor, D., Olson, D., Olson, K., Ortega, A., Ossi, F., Panzacchi, M., Patchett, R., Patterson, B., Paula, R. C. D., Payne, J., Peters, W., Petroelje, T., Pitcher, B., Pokorny, B., Poole, K., Potočnik, H., Poulin, M.-P., Pringle, R., Prins, H., Ranc, N., Reljić, S., Robb, B., Röder, R., Rolandsen, C., Rutz, C., Salemgareyev, A., Samelius, G., Sayine-Crawford, H., Schooler, S., Şekercioğlu, Ç., Selva, N., Semenzato, P., Sergiel, A., Sharma, K., Shawler, A., Signer, J., Silovský, V., Silva, J., Simon, R., Smiley, R., Smith, D., Solberg, E., Soto, D., Spiegel, O., Stabach, J., Stacy-Dawes, J., Stahler, D., Stephenson, J., Stewart, C., Strand, O., Sunde, P., Svoboda, N., Swart, J., Thompson, J., Toal, K., Uiseb, K., Vanacker, M., Velilla, M., Verzuh, T., Wachter, B., Wagler, B., Whittington, J., Wikelski, M., Wilmers, C., Wittemyer, G., Young, J., Zięba, F., Zwijacz-Kozica, T., Huijbregts, M., and Mueller, T.

Abstract

COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals’ 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.

Published
2023

8. The search behavior of terrestrial mammals

Author

Noonan, M. J., (0000-0003-2765-8147) Martinez Garcia, R., Fleming, C. H., Garcia De Figueiredo, B., Ali, A. H., Attias, N., Belant, J. L., Beyer Jr., D. E., Berteaux, D., Bidner, L. R., Boone, R., Boutin, S., Brito, J., Brown, M., Carter, A., Castellanos, A., Castellanos, F. X., Chitwood, C., Darlington, S., Antonio De La Torre, J., Dekker, J., Deperno, C., Droghini, A., Farhadinia, M., Fennessy, J., Fichtel, C., Ford, A., Gill, R., Goheen, J. R., Gustavo R. Oliveira-Santos, L., Hebblewhite, M., Hodges, K. E., Isbell, L. A., Janssen, R., Kappeler, P., Kays, R., Kaczensky, P., Kauffman, M., Lapoint, S., Alan Lashley, M., Leimgruber, P., Little, A., Macdonald, D. W., Masiaine, S., T. McBride Jr., R., Patricia Medici, E., Mertes, K., Moorman, C., Morato, R. G., Mourão, G., Mueller, T., Neilson, E. W., Pastorini, J., Patterson, B. D., Pereira, J., Petroelje, T. R., Piecora, K., John Power, R., Rachlow, J., Ranglack, D. H., Roshier, D., Safford, K., Scott, D. M., Serrouya, R., Songer, M., Songsasen, N., Stabach, J., Stacy-Dawes, J., Swingen, M. B., Thompson, J., Tucker, M. A., Velilla, M., Yarnell, R. W., Young, J., Fagan, W. F., (0000-0003-0575-6408) Calabrese, J., Noonan, M. J., (0000-0003-2765-8147) Martinez Garcia, R., Fleming, C. H., Garcia De Figueiredo, B., Ali, A. H., Attias, N., Belant, J. L., Beyer Jr., D. E., Berteaux, D., Bidner, L. R., Boone, R., Boutin, S., Brito, J., Brown, M., Carter, A., Castellanos, A., Castellanos, F. X., Chitwood, C., Darlington, S., Antonio De La Torre, J., Dekker, J., Deperno, C., Droghini, A., Farhadinia, M., Fennessy, J., Fichtel, C., Ford, A., Gill, R., Goheen, J. R., Gustavo R. Oliveira-Santos, L., Hebblewhite, M., Hodges, K. E., Isbell, L. A., Janssen, R., Kappeler, P., Kays, R., Kaczensky, P., Kauffman, M., Lapoint, S., Alan Lashley, M., Leimgruber, P., Little, A., Macdonald, D. W., Masiaine, S., T. McBride Jr., R., Patricia Medici, E., Mertes, K., Moorman, C., Morato, R. G., Mourão, G., Mueller, T., Neilson, E. W., Pastorini, J., Patterson, B. D., Pereira, J., Petroelje, T. R., Piecora, K., John Power, R., Rachlow, J., Ranglack, D. H., Roshier, D., Safford, K., Scott, D. M., Serrouya, R., Songer, M., Songsasen, N., Stabach, J., Stacy-Dawes, J., Swingen, M. B., Thompson, J., Tucker, M. A., Velilla, M., Yarnell, R. W., Young, J., Fagan, W. F., and (0000-0003-0575-6408) Calabrese, J.

Abstract

Animals moving through landscapes need to strike a balance between finding sufficient resources to grow and reproduce while minimizing encounters with predators 1,2. Because encounter rates are determined by the average distance over which directed motion persists 1,3–5, this trade-off should be apparent in individuals’ movement. Using GPS data from 1,396 individuals across 62 species of terrestrial mammals, we show how predators maintained directed motion ~7 times longer than for similarly-sized prey, revealing how prey species must trade off search efficiency against predator encounter rates. Individual search strategies were also modulated by resource abundance, with prey species forced to risk higher predator encounter rates when resources were scarce. These findings highlight the interplay between encounter rates and resource availability in shaping broad patterns mammalian movement strategies.

Published
2023

20. Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma

Author

Shah, J., Shacham, S., Kauffman, M., Daniele, P., Tomaras, D., Tremblay, G., Casasnovas, R.O., Maerevoet, M., Zijlstra, J., Follows, G., Vermaat, J.S.P., Kalakonda, N., Goy, A.H., Choquet, S., Neste, E. van den, Hill, B.T., Thieblemont, C., Cavallo, F., Cruz, F. de la, Kuruvilla, J., Hamad, N., Bouabdallah, R., Jager, U., Caimi, P., Gurion, R., Warzocha, K., Bakhshi, S., Sancho, J.M., Schuster, M., Egyed, M., Offner, F., Vasilakopoulos, T.P., Samal, P., Nagy, A., Ku, M., and Albendea, M.A.C.

Subjects
health-related quality of life, disutility of adverse events, EQ-5D-5L, diffuse large B-cell lymphoma, health utility, FACT-Lym, patient reported outcomes, health state utility, selinexor
Abstract

Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p = 3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts.

Published
2021

24. Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C

Author

Pelletier, F. Perrier, S. Cayami, F.K. Mirchi, A. Saikali, S. Tran, L.T. Ulrick, N. Guerrero, K. Rampakakis, E. Van Spaendonk, R.M.L. Naidu, S. Pohl, D. Gibson, W.T. Demos, M. Goizet, C. Tejera-Martin, I. Potic, A. Fogel, B.L. Brais, B. Sylvain, M. Sébire, G. Lourenço, C.M. Bonkowsky, J.L. Catsman-Berrevoets, C. Pinto, P.S. Tirupathi, S. Strømme, P. De Grauw, T. Gieruszczak-Bialek, D. Krägeloh-Mann, I. Mierzewska, H. Philippi, H. Rankin, J. Atik, T. Banwell, B. Benko, W.S. Blaschek, A. Bley, A. Boltshauser, E. Bratkovic, D. Brozova, K. Cimas, I. Clough, C. Corenblum, B. Dinopoulos, A. Dolan, G. Faletra, F. Fernandez, R. Fletcher, J. Garcia Garcia, M.E. Gasparini, P. Gburek-Augustat, J. Gonzalez Moron, D. Hamati, A. Harting, I. Hertzberg, C. Hill, A. Hobson, G.M. Innes, A.M. Kauffman, M. Kirwin, S.M. Kluger, G. Kolditz, P. Kotzaeridou, U. La Piana, R. Liston, E. McClintock, W. McEntagart, M. McKenzie, F. Melançon, S. Misbahuddin, A. Suri, M. Monton, F.I. Moutton, S. Murphy, R.P.J. Nickel, M. Onay, H. Orcesi, S. Özklnay, F. Patzer, S. Pedro, H. Pekic, S. Pineda Marfa, M. Pizzino, A. Plecko, B. Poll-The, B.T. Popovic, V. Rating, D. Rioux, M.-F. Rodriguez Espinosa, N. Ronan, A. Ostergaard, J.R. Rossignol, E. Sanchez-Carpintero, R. Schossig, A. Senbil, N. Sønderberg Roos, L.K. Stevens, C.A. Synofzik, M. Sztriha, L. Tibussek, D. Timmann, D. Tonduti, D. Van De Warrenburg, B.P. Vázquez-López, M. Venkateswaran, S. Wasling, P. Wassmer, E. Webster, R.I. Wiegand, G. Yoon, G. Rotteveel, J. Schiffmann, R. Van Der Knaap, M.S. Vanderver, A. Martos-Moreno, G.Á. Polychronakos, C. Wolf, N.I. Bernard, G.

Abstract

Context: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting: This was a multicenter retrospective study using information collected from 3 predominant centers. Patients: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder. © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.

Published
2021

25. Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma

Author

Shah, J. Shacham, S. Kauffman, M. Daniele, P. Tomaras, D. Tremblay, G. Casasnovas, R.-O. Maerevoet, M. Zijlstra, J. Follows, G. P Vermaat, J.S. Kalakonda, N. Goy, A.H. Choquet, S. Den Neste, E.V. Hill, B.T. Thieblemont, C. Cavallo, F. La Cruz, F.D. Kuruvilla, J. Hamad, N. Bouabdallah, R. Jäger, U. Caimi, P. Gurion, R. Warzocha, K. Bakhshi, S. Sancho, J.M. Schuster, M. Egyed, M. Offner, F. Vasilakopoulos, T.P. Samal, P. Nagy, A. Ku, M. Canales Albendea, M.Á.

Abstract

Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT)-Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT-Lymphoma (p ≤ 0.05), FACT-General (p < 0.05) and EuroQoL five-dimensions five-levels index scores (p < 0.001) beginning in cycle 3. The estimated difference in health state utilities for treatment response and progressive disease was both statistically significant and clinically meaningful (mean difference: 0.07; p = 0.001). Conclusion: In patients with relapsed/refractory diffuse large B-cell lymphoma, objective response to selinexor was associated with HRQoL maintenance, reduction in disease-related HRQoL decrements and higher health utilities. © 2021 Patrick Daniele.

Published
2021

26. Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma

Author

Shah, J, Shacham, S, Kauffman, M, Daniele, P, Tomaras, D, Tremblay, G, Casasnovas, RO, Maerevoet, M, Zijlstra, J, Follows, G, Vermaat, JSP, Kalakonda, N, Goy, AH, Choquet, S, Van den Neste, E, Hill, BT, Thieblemont, C, Cavallo, F, de la Cruz, F, Kuruvilla, J, Hamad, N, Bouabdallah, R, Jager, U, Caimi, P, Gurion, R, Warzocha, K, Bakhshi, S, Sancho, JM, Schuster, M, Egyed, M, Offner, F, Vasilakopoulos, TP, Samal, P, Nagy, A, Ku, M, and Albendea, MAC

Subjects
health-related quality of life, disutility of adverse events, EQ-5D-5L, diffuse large B-cell lymphoma, health utility, FACT-Lym, patient reported outcomes, health state utility, selinexor
Abstract

Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p = 3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts.

Published
2021

27. Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C

Author

Pelletier, F., Perrier, S., Cayami, F.K., Mirchi, A., Saikali, S., Tran, L.T., Ulrick, N., Guerrero, K., Rampakakis, E., Spaendonk, R.M.L. van, Naidu, S., Pohl, D., Gibson, W.T., Demos, M., Goizet, C., Tejera-Martin, I., Potic, A., Fogel, B.L., Brais, B., Sylvain, M., Sébire, G., Lourenço, C.M., Bonkowsky, J.L., Catsman-Berrevoets, C., Pinto, P.S., Tirupathi, S., Strømme, P., Grauw, T. de, Gieruszczak-Bialek, D., Krägeloh-Mann, I., Mierzewska, H., Philippi, H., Rankin, J., Atik, T., Banwell, B., Benko, W.S., Blaschek, A., Bley, A., Boltshauser, E., Bratkovic, D., Brozova, K., Cimas, I., Clough, C., Corenblum, B., Dinopoulos, A., Dolan, G., Faletra, F., Fernandez, R., Fletcher, J., Garcia, M.E., Gasparini, P., Gburek-Augustat, J., Moron, D. Gonzalez, Hamati, A., Harting, I., Hertzberg, C., Hill, A., Hobson, G.M., Innes, A. Micheil, Kauffman, M., Kirwin, S.M., Kluger, G., Kolditz, P., Kotzaeridou, U., Piana, R., Liston, E., McClintock, W., McEntagart, M., McKenzie, F., Melançon, S., Misbahuddin, A., Suri, M., Monton, F.I., Moutton, S., Murphy, R.P.J., Nickel, M., Onay, H., Orcesi, S., Özkınay, F., Patzer, S., Pedro, H., Pekic, S., Marfa, M. Pineda, Pizzino, A., Plecko, B., Poll-The, B.T., Popovic, V., Rating, D., Rioux, M.F., Espinosa, N. Rodriguez, Ronan, A., Ostergaard, J.R., Rossignol, E., Sanchez-Carpintero, R., Schossig, A., Senbil, N., Roos, L.K. Sønderberg, Stevens, C.A., Synofzik, M., Sztriha, L., et al., Warrenburg, B.P.C. van de, Wolf, N.I., Bernard, G., Pelletier, F., Perrier, S., Cayami, F.K., Mirchi, A., Saikali, S., Tran, L.T., Ulrick, N., Guerrero, K., Rampakakis, E., Spaendonk, R.M.L. van, Naidu, S., Pohl, D., Gibson, W.T., Demos, M., Goizet, C., Tejera-Martin, I., Potic, A., Fogel, B.L., Brais, B., Sylvain, M., Sébire, G., Lourenço, C.M., Bonkowsky, J.L., Catsman-Berrevoets, C., Pinto, P.S., Tirupathi, S., Strømme, P., Grauw, T. de, Gieruszczak-Bialek, D., Krägeloh-Mann, I., Mierzewska, H., Philippi, H., Rankin, J., Atik, T., Banwell, B., Benko, W.S., Blaschek, A., Bley, A., Boltshauser, E., Bratkovic, D., Brozova, K., Cimas, I., Clough, C., Corenblum, B., Dinopoulos, A., Dolan, G., Faletra, F., Fernandez, R., Fletcher, J., Garcia, M.E., Gasparini, P., Gburek-Augustat, J., Moron, D. Gonzalez, Hamati, A., Harting, I., Hertzberg, C., Hill, A., Hobson, G.M., Innes, A. Micheil, Kauffman, M., Kirwin, S.M., Kluger, G., Kolditz, P., Kotzaeridou, U., Piana, R., Liston, E., McClintock, W., McEntagart, M., McKenzie, F., Melançon, S., Misbahuddin, A., Suri, M., Monton, F.I., Moutton, S., Murphy, R.P.J., Nickel, M., Onay, H., Orcesi, S., Özkınay, F., Patzer, S., Pedro, H., Pekic, S., Marfa, M. Pineda, Pizzino, A., Plecko, B., Poll-The, B.T., Popovic, V., Rating, D., Rioux, M.F., Espinosa, N. Rodriguez, Ronan, A., Ostergaard, J.R., Rossignol, E., Sanchez-Carpintero, R., Schossig, A., Senbil, N., Roos, L.K. Sønderberg, Stevens, C.A., Synofzik, M., Sztriha, L., et al., Warrenburg, B.P.C. van de, Wolf, N.I., and Bernard, G.

Abstract

Contains fulltext : 235629.pdf (Publisher’s version ) (Open Access), CONTEXT: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. OBJECTIVE: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. DESIGN: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. SETTING: This was a multicenter retrospective study using information collected from 3 predominant centers. PATIENTS: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. MAIN OUTCOME MEASURES: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. RESULTS: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. CONCLUSIONS: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.

Published
2021

28. Peripheral neuropathy symptoms, pain, and functioning in previously treated multiple myeloma patients treated with selinexor, bortezomib, and dexamethasone

Author

Sanchez, L, Leleu, X, Beaumont, JL, Yu, H, Hudgens, S, Simonova, M, Auner, HW, Quach, H, Delimpasi, S, Spicka, I, Pour, L, Kriachok, I, Dimopoulos, MA, Usenko, G, Hajek, R, Benjamin, R, Sinha, DK, Venner, C, Illmer, T, Garg, MK, Stevens, DA, Jagannath, S, Levy, M, Anderson, LD, Bahlis, NJ, Facon, T, Cavo, M, Chai, Y, Ma, X, Tang, S, Leong, H, Shah, J, Shacham, S, Kauffman, M, Richardson, P, Grosicki, S, Sanchez, L, Leleu, X, Beaumont, JL, Yu, H, Hudgens, S, Simonova, M, Auner, HW, Quach, H, Delimpasi, S, Spicka, I, Pour, L, Kriachok, I, Dimopoulos, MA, Usenko, G, Hajek, R, Benjamin, R, Sinha, DK, Venner, C, Illmer, T, Garg, MK, Stevens, DA, Jagannath, S, Levy, M, Anderson, LD, Bahlis, NJ, Facon, T, Cavo, M, Chai, Y, Ma, X, Tang, S, Leong, H, Shah, J, Shacham, S, Kauffman, M, Richardson, P, and Grosicki, S

Published
2021

30. Selinexor in patients with relapsed or refractory diffuse large B -cell lymphoma (SADAL): a single -arm, multinational, multicentre, open -label, phase 2 trial

Author

Kalakonda, N., Maerevoet, M., Cavallo, F., Follows, G., Goy, A., Vermaat, J.S.P., Casasnovas, O., Hamad, N., Zijlstra, J.M., Bakhshi, S., Bouabdallah, R., Choquet, S., Gurion, R., Hill, B., Jaeger, U., Sancho, J.M., Schuster, M., Thieblemont, C., Cruz, F. de la, Egyed, M., Mishra, S., Offner, F., Vassilakopoulos, T.P., Warzocha, K., McCarthy, D., Ma, X.W., Corona, K., Saint-Martin, J.R., Chang, H., Landesman, Y., Joshi, A., Wang, H.W., Shah, J., Shacham, S., Kauffman, M., Neste, E. van den, and Canales, M.A.

Abstract

Background Relapsed or refractory diffuse large B -cell lymphoma (DLBCL) is an aggressive cancer with a median overall survival of less than 6 months. We aimed to assess the response to single -agent selinexor, an oral selective inhibitor of nuclear export, in patients with relapsed or refractory DLBCL who had no therapeutic options of potential clinical benefit. Methods SADAL was a multicentre, multinational, open -label, phase 2b study done in 59 sites in 19 countries. Patients aged 18 years or older with pathologically confirmed diffuse large B -cell lymphoma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received two to five lines of previous therapies, and progressed after or were not candidates for autologous stem -cell transplantation were enrolled. Germinal centre B -cell or non -germinal centre B -cell tumour subtype and double or triple expressor status were determined by immunohistochemistry and double or triple hit status was determined by cytogenetics. Patients received 60 mg selinexor orally on days 1 and 3 weekly until disease progression or unacceptable toxicity. The study was initially designed to evaluate both 60 mg and 100 mg twice -weekly doses of selinexor; however, the 100 mg dose was discontinued in the protocol (version 7.0) on March 29, 2017, when an improved therapeutic window was observed at 60 mg. Primary outcome was overall response rate. The primary outcome and safety were assessed in all patients who received 60 mg selinexor under protocol version 6.0, or enrolled under protocol versions 7.0 or higher and received at least one dose of selinexor. This trial is registered at ClinicalTrials.gov, NCT02227251 (active but not enrolling). Findings Between Oct 21, 2015, and Nov 2, 2019, 267 patients were randomly assigned, with 175 allocated to the 60 mg group and 92 to the discontinued 100 mg group. 48 patients assigned to the 60 mg group were excluded due to enrolment before version 6.0 of the protocol; the remaining 127 patients received selinexor 60 mg and were included in analyses of primary outcome and safety. The overall response rate was 28% (36/127; 95% CI 20?7-37?0); 15 (12%) achieved a complete response and 21 (17%) a partial response. The most common grade 3-4 adverse events were thrombocytopenia (n=58), neutropenia (n=31), anaemia (n=28), fatigue (n=14), hyponatraemia (n=10), and nausea (n=8). The most common serious adverse events were pyrexia (n=9), pneumonia (n=6), and sepsis (n=6). There were no deaths judged as related to treatment with selinexor. Interpretation Single -drug oral selinexor induced durable responses and had a manageable adverse events profile in patients with relapsed or refractory DLBCL who received at least two lines of previous chemoimmunotherapy. Selinexor could be considered a new oral, non-cytotoxic treatment option in this setting.

Published
2020

31. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial

Author

Kalakonda, N. Maerevoet, M. Cavallo, F. Follows, G. Goy, A. Vermaat, J.S.P. Casasnovas, O. Hamad, N. Zijlstra, J.M. Bakhshi, S. Bouabdallah, R. Choquet, S. Gurion, R. Hill, B. Jaeger, U. Sancho, J.M. Schuster, M. Thieblemont, C. De la Cruz, F. Egyed, M. Mishra, S. Offner, F. Vassilakopoulos, T.P. Warzocha, K. McCarthy, D. Ma, X. Corona, K. Saint-Martin, J.-R. Chang, H. Landesman, Y. Joshi, A. Wang, H. Shah, J. Shacham, S. Kauffman, M. Van Den Neste, E. Canales, M.A.

Abstract

Background: Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer with a median overall survival of less than 6 months. We aimed to assess the response to single-agent selinexor, an oral selective inhibitor of nuclear export, in patients with relapsed or refractory DLBCL who had no therapeutic options of potential clinical benefit. Methods: SADAL was a multicentre, multinational, open-label, phase 2b study done in 59 sites in 19 countries. Patients aged 18 years or older with pathologically confirmed diffuse large B-cell lymphoma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received two to five lines of previous therapies, and progressed after or were not candidates for autologous stem-cell transplantation were enrolled. Germinal centre B-cell or non-germinal centre B-cell tumour subtype and double or triple expressor status were determined by immunohistochemistry and double or triple hit status was determined by cytogenetics. Patients received 60 mg selinexor orally on days 1 and 3 weekly until disease progression or unacceptable toxicity. The study was initially designed to evaluate both 60 mg and 100 mg twice-weekly doses of selinexor; however, the 100 mg dose was discontinued in the protocol (version 7.0) on March 29, 2017, when an improved therapeutic window was observed at 60 mg. Primary outcome was overall response rate. The primary outcome and safety were assessed in all patients who received 60 mg selinexor under protocol version 6.0, or enrolled under protocol versions 7.0 or higher and received at least one dose of selinexor. This trial is registered at ClinicalTrials.gov, NCT02227251 (active but not enrolling). Findings: Between Oct 21, 2015, and Nov 2, 2019, 267 patients were randomly assigned, with 175 allocated to the 60 mg group and 92 to the discontinued 100 mg group. 48 patients assigned to the 60 mg group were excluded due to enrolment before version 6.0 of the protocol; the remaining 127 patients received selinexor 60 mg and were included in analyses of primary outcome and safety. The overall response rate was 28% (36/127; 95% CI 20·7–37·0); 15 (12%) achieved a complete response and 21 (17%) a partial response. The most common grade 3–4 adverse events were thrombocytopenia (n=58), neutropenia (n=31), anaemia (n=28), fatigue (n=14), hyponatraemia (n=10), and nausea (n=8). The most common serious adverse events were pyrexia (n=9), pneumonia (n=6), and sepsis (n=6). There were no deaths judged as related to treatment with selinexor. Interpretation: Single-drug oral selinexor induced durable responses and had a manageable adverse events profile in patients with relapsed or refractory DLBCL who received at least two lines of previous chemoimmunotherapy. Selinexor could be considered a new oral, non-cytotoxic treatment option in this setting. Funding: Karyopharm Therapeutics Inc. © 2020 Elsevier Ltd

Published
2020

32. Effects of body size on estimation of mammalian area requirements

Author

Noonan, M.J., Fleming, C.H., Tucker, M.A., Kays, R., Harrison, A.L., Crofoot, M.C., Abrahms, B., Alberts, S.C., Ali, A.H., Altmann, J., Antunes, P.C., Attias, N., Belant, J.L., Beyer, D.E., Jr., Bidner, L.R., Blaum, N., Boone, R.B., Caillaud, D., Paula, R.C. de, Torre, J.A. de la, Dekker, J., DePerno, C.S., Farhadinia, M., Fennessy, J., Fichtel, C., Fischer, C., Ford, A., Goheen, J.R., Havmoller, R.W., Hirsch, B.T., Hurtado, C., Isbell, L.A., Janssen, Rene, Jeltsch, F., Kaczensky, P., Kaneko, Y., Kappeler, P., Katna, A., Kauffman, M., Koch, F., Kulkarni, A., LaPoint, S., Leimgruber, P., Macdonald, D.W., Markham, A.C., McMahon, L., Mertes, K., Moorman, C.E., Morato, R.G., Mossbrucker, A.M., Mourao, G., O'Connor, D., Oliveira-Santos, L.G.R., Pastorini, J., Patterson, B.D., Rachlow, J., Ranglack, D.H., Reid, N., Scantlebury, D.M., Scott, D.M., Selva, N., Sergiel, A., Songer, M., Songsasen, N., Stabach, J.A., Stacy-Dawes, J., Swingen, M.B., Thompson, J.J., Ullmann, W., Vanak, A.T., Thaker, M., Wilson, J.W., Yamazaki, K., Yarnell, R.W., Zieba, F., Zwijacz-Kozica, T., Fagan, W.F., Mueller, T., Calabrese, J.M., Noonan, M.J., Fleming, C.H., Tucker, M.A., Kays, R., Harrison, A.L., Crofoot, M.C., Abrahms, B., Alberts, S.C., Ali, A.H., Altmann, J., Antunes, P.C., Attias, N., Belant, J.L., Beyer, D.E., Jr., Bidner, L.R., Blaum, N., Boone, R.B., Caillaud, D., Paula, R.C. de, Torre, J.A. de la, Dekker, J., DePerno, C.S., Farhadinia, M., Fennessy, J., Fichtel, C., Fischer, C., Ford, A., Goheen, J.R., Havmoller, R.W., Hirsch, B.T., Hurtado, C., Isbell, L.A., Janssen, Rene, Jeltsch, F., Kaczensky, P., Kaneko, Y., Kappeler, P., Katna, A., Kauffman, M., Koch, F., Kulkarni, A., LaPoint, S., Leimgruber, P., Macdonald, D.W., Markham, A.C., McMahon, L., Mertes, K., Moorman, C.E., Morato, R.G., Mossbrucker, A.M., Mourao, G., O'Connor, D., Oliveira-Santos, L.G.R., Pastorini, J., Patterson, B.D., Rachlow, J., Ranglack, D.H., Reid, N., Scantlebury, D.M., Scott, D.M., Selva, N., Sergiel, A., Songer, M., Songsasen, N., Stabach, J.A., Stacy-Dawes, J., Swingen, M.B., Thompson, J.J., Ullmann, W., Vanak, A.T., Thaker, M., Wilson, J.W., Yamazaki, K., Yarnell, R.W., Zieba, F., Zwijacz-Kozica, T., Fagan, W.F., Mueller, T., and Calabrese, J.M.

Abstract

Contains fulltext : 226766.pdf (publisher's version ) (Open Access)

Published
2020

33. Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies

Author

Vergote, I. B., Lund, B., Peen, U., Umajuridze, Z., Mau-Sorensen, M., Kranich, A., Van Nieuwenhuysen, E., Haslund, C., Nottrup, T., Han, S. N., Concin, N., Unger, T. J., Chai, Y., Au, N., Rashal, T., Joshi, A., Crochiere, M., Landesman, Y., Shah, J., Shacham, S., Kauffman, M., Mirza, M. R., Vergote, I. B., Lund, B., Peen, U., Umajuridze, Z., Mau-Sorensen, M., Kranich, A., Van Nieuwenhuysen, E., Haslund, C., Nottrup, T., Han, S. N., Concin, N., Unger, T. J., Chai, Y., Au, N., Rashal, T., Joshi, A., Crochiere, M., Landesman, Y., Shah, J., Shacham, S., Kauffman, M., and Mirza, M. R.

Abstract

Background: Selinexor is an oral inhibitor of the nuclear export protein Exportin 1 (XPO1) with demonstrated antitumor activity in solid and hematological malignancies. We evaluated the efficacy and safety of selinexor in heavily pretreated, recurrent gynecological malignancies. Methods: In this phase 2 trial, patients received selinexor (35 or 50 mg/m2 twice-weekly [BIW] or 50 mg/m2 once-weekly [QW]) in 4-week cycles. Primary endpoint was disease control rate (DCR) including complete response (CR), partial response (PR) or stable disease (SD) ≥12 weeks. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results: 114 patients with ovarian (N = 66), endometrial (N = 23) or cervical (N = 25) cancer were enrolled. Median number of prior regimens for ovarian, endometrial and cervical cancer was 6 (1–11), 2 (1–5), and 3 (1–6) respectively. DCR was 30% (ovarian 30%; endometrial 35%; cervical 24%), which included confirmed PRs in 8%, 9%, and 4% of patients with ovarian, endometrial, and cervical cancer respectively. Median PFS and OS for patients with ovarian, endometrial and cervical cancer were 2.6, 2.8 and 1.4 months, and 7.3, 7.0, and 5.0 months, respectively. Common Grade 3/4 adverse events (AEs) were thrombocytopenia (17%), fatigue (14%), anemia (10%), nausea (9%) and hyponatremia (9%). Patients with ovarian cancer receiving 50 mg/m2 QW had fewer high-grade AEs with similar efficacy as BIW treatment. Conclusions: Selinexor demonstrated single-agent activity and disease control in patients with heavily pretreated ovarian and endometrial cancers. Side effects were a function of dose level and treatment frequency, similar to previous reports, reversible and mitigated with supportive care.

Published
2020

40. Stereoselective Reactions of Carbonyl and Imino Groups

Author

Molander, G. A., primary, Molander, G. A., additional, Arai, N., additional, Ohkuma, T., additional, Carreira, E. M., additional, Frantz, D. E., additional, Aschwanden, P., additional, Bergin, E., additional, Liu, L., additional, Wang, D., additional, Li, C. -J., additional, Yliniemelä-Sipari, S. M., additional, Pihko, P. M., additional, Clapés, P., additional, Fessner, W. -D., additional, Masson, G., additional, Zhu, J., additional, Burns, N. Z., additional, Jacobsen, E. N., additional, DiRocco, D. A., additional, Rovis, T., additional, Carter, R. G., additional, Kuiper, D. L., additional, Zaidlewicz, M., additional, Pakulski, M. M., additional, De Wildeman, S., additional, Sereinig, N., additional, Stoltz, B., additional, Ebner, D. C., additional, Park, N., additional, Xu, L., additional, Wu, X., additional, Xiao, J., additional, Aggarwal, V. K., additional, McGarrigle, E. M., additional, Shaw, M. A., additional, Ramón, D. J., additional, Yus, M., additional, Buitrago Santanilla, A., additional, Leighton, J. L., additional, Kauffman, M. C., additional, and Walsh, P. J., additional

Published
2011
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results