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155. DFT calculation of four new potential agents muscarinic of bispyridinium type: structure, synthesis, biological activity, hydration, and relations with the potents W84 and DUO-3O.

Author

Palafox, M. Alcolea, Posada-Moreno, P., Villarino-Marín, A. L., Martinez-Rincon, C., Ortuño-Soriano, I., and Zaragoza-García, I.

Subjects
DENSITY functionals, MUSCARINIC receptors, CHOLINERGIC receptors, ALLOSTERIC enzymes, SIMULATION methods & models
Abstract

Four new potential agents muscarinic (allosteric modulators) were synthesized and studied by using the B3LYP density functional method. The optimum conformation and geometry structure of these compounds were determined and analyzed. Solvent effects were considered including a variable number (1-15) of explicit water molecules surrounding the compound in order to simulate the first hydration shell, as well as using the Tomasi's polarized continuum model (PCM). A similar simultaneous analysis of the potents W84 and DUO-3O allosteric modulator of muscarinic receptors was also carried out. The effect of the hydration on the total atomic charges and several intermolecular distances of interest were also discussed. The biological activity against acetylcholine of our four synthesized bispyridinium salts was determined. Relationships/tendencies structure-activity were established. Several general conclusions were underlined. [ABSTRACT FROM AUTHOR]

Published
2011
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158. Vibrational frequencies and structure of 2-thiouracil by Hartree–Fock, post-Hartree–Fock and density functional methods

Author

Palafox, M. Alcolea, Rastogi, V.K., Tanwar, R.P., and Mittal, Lalit

Subjects
*VIBRATION (Mechanics), *BIOMOLECULES, *DENSITY functionals, *URACIL, *RAMAN effect
Abstract

Vibrational study of the biomolecule 2-thiouracil was carried out. Ab initio and density functional calculations were performed to assign the experimental spectra. A comparison with the uracil molecule was made, and specific scale factors were deduced and employed in the predicted frequencies of 2-thiouracil. Several scaling procedures were used. The geometry structure of the molecule was determined. The effect of sulfur substitution at C2 position in the uracil molecule, on the N1&z.sbnd;H and N3&z.sbnd;H frequencies and intensities reflects changes in proton donor abilities of these groups. Calculations with the 6-31 G** basis set with HF and DFT methods appear in general to be useful for interpretation of the general features of the IR and Raman spectra of the molecule. Using specific scale factors a very small error was obtained. The use of these specific scale factors resolve and correct some of the controversial assignments in the literature. [Copyright &y& Elsevier]

Published
2003
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160. 3,5-Difluorobenzonitrile: ab initio calculations, FTIR and Raman spectra

Author

Rastogi, V.K., Palafox, M. Alcolea, Tanwar, R.P., and Mittal, Lalit

Subjects
*VIBRATIONAL spectra, *QUANTUM chemistry, *RAMAN effect
Abstract

Geometry, vibrational wavenumbers and several thermodynamic parameters were calculated using ab initio quantum chemical methods for the 3,5-difluorobenzonitrile molecule. The results were compared with the experimental values. With the help of three specific scaling procedures, the observed vibrational wavenumbers in FTIR and Raman spectra were analysed and assigned to different normal modes of the molecule. Most of the modes have wavenumbers in the expected range and the error obtained was in general very low. Using PEDs the contributions were determined for the different modes to each wavenumber. From the PED, it is apparent that the frequency corresponding to C&z.tbnd6;N stretching contains 87% contribution from the C&z.tbnd6;N stretching force constant and it mixes with the C&z.sbnd;CN stretching mode 13 to the extent of 12%. Other general conclusions were also deduced. [ABSTRACT FROM AUTHOR]

Published
2002
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162. Molecular structure differences between the antiviral Nucleoside Analogue 5-iodo-2′-deoxyuridine and the natural nucleoside 2′-deoxythymidine using MP2 and DFT methods: conformational analysis, crystal simulations, DNA pairs and possible behaviour

Author

Alcolea Palafox, M.

Abstract

5-iodo-2′-deoxyuridine Nucleoside Analogue (IUdR) was the first selective antiviral nucleoside against herpes simplex virus type 1 and 2, and it was also a meaningful anticancer drug. Within a full study of this drug and its possible behaviour, previously, a comprehensive theoretical conformational analysis by MP2 and B3LYP was carried out, and all the possible stable structures were determined with full relaxation of all geometrical parameters. The search located 45 stable structures, and in all them, the whole conformational parameters (, , , , , P, max) were analyzed as well as the NBO natural atomic charges. Comparisons of the conformers with those of the natural Nucleoside 2′-deoxythymidine (dT) were carried out, and the main differences between IUdR and dT were analyzed. The accuracy of the methods used was probed with the simulation of the X-ray crystal data by a tetramer form. Watson-Crick (WC) IUdR/dT···2′-deoxyadenosine pairs were analyzed for the first time using quantum chemical calculations, as well as the mispairing IUdR/dT···2′-deoxyguanosine. As result, it is observed that IUdR give rises to a slightly stronger WC pair and weaker mispairing than those with dT, therefore deforming slightly the DNA axis and difficulting the growth of the DNA virus and consequently, killing it.

Published
2014
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163. El turismo y el agua como ejes de acumulación en Ixtapan de la Sal, México

Author

Hernández Peñaloza, Nadia, Zizumbo Villarreal, Lilia, Palafox Muñoz, Alejandro, and Vargas Martínez, Elva Esther

Subjects
Recreation. Leisure, GV1-1860
Abstract

En la lógica de expansión y reproducción del capital, los países en vías de desarrollo son insertados en actividades turísticas con la intención de mejorar sus condiciones de vida, sin embargo, esta inserción se realiza mediante la explotación de sus recursos, especialmente los naturales, mismos que son utilizados como mercancía, de manera que pueden ser comercializados y manipulados a favor de la iniciativa privada en colaboración con el Estado. Tal es el caso del municipio de Ixtapan de la Sal, México, donde la población ha sido despojada del recurso agua, concesionada por parte del Gobierno a una empresa particular, que la utiliza para funcionamiento de empresas orientadas al uso turístico y quien se encarga de abastecer a la población, siendo esta organización la más favorecida por el desarrollo de la actividad, esto ha sido posible gracias a las estrechas relaciones que se han construido y fortalecido con el paso de los años con actores clave, con lo cual generan riquezas que solo han beneficiado a particulares, dejando a la población al margen y limitando sus actividades económicas. Pero sobre todo ha delimitado el tipo de turismo que se quiere mantener en el lugar, instaurando una comunidad aislada de la obtención de ganancias, que en otras condiciones pudieron haber obtenido mejores oportunidades de crecimiento económico y de calidad de vida.

Published
2020
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165. Research report. The quality of private and public primary health care management of children with diarrhoea and acute respiratory infections in Tlaxcala, Mexico.

Author

Bojalil, R, Guiscafré, H, Espinosa, P, Martínez, H, Palafox, M, Romero, G, and Guttiérez, G

Abstract

In Tlaxcala, Mexico, 80% of the children who died from diarrhoea or acute respiratory infections (ARI) in 1992-1993 received medical care; in more than 70% of cases it was provided by a private general practitioner (GP). The present study evaluated the quality of case management by private and public GPs to children under five years of age with diarrhoea and ARI. During the clinical observation, the treatment and counselling given to the mother were assessed with the WHO guidelines as reference standard. A total of 41 private and 40 public GPs were evaluated for the management of diarrhoea, and 59 private and 40 public GPs for the management of ARI. For diarrhoea, half of the private GPs gave inadequate rehydration therapy, 63% gave incorrect advice on diet, 66% and 49% made an incorrect decision in the prescription of antimicrobial and symptomatic drugs, respectively. Public GPs generally performed better in diarrhoea management: 7% gave inadequate rehydration therapy, 13% gave wrong advice on diet, 3% made a wrong decision in the prescription of symptomatic drugs and 28% gave a wrong decision in antimicrobial prescription. In the management of ARI, 66% and 58% of private GPs made a wrong decision in the prescription of antimicrobial and symptomatic drugs, respectively, compared to 30% and 20% of public GPs, respectively. Counselling to the mother given by both private and public GPs was considered inadequate in most cases of diarrhoea and ARI. These results clearly show that private doctors, as important providers of medical care, need to be included in the strategies to improve the quality of care of children with diarrhoea and ARI. Future research needs to address the determinants of the clinical practice of private doctors in countries like Mexico. [ABSTRACT FROM PUBLISHER]

Published
1998
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166. The quality of private and public primary health care management of children with diarrhoea and acute respiratory infections in Tlaxcala, Mexico.

Author

Bojalil, R, Guiscafré, H, Espinosa, P, Martínez, H, Palafox, M, Romero, G, and Gutiérrez, G

Abstract

In Tlaxcala, Mexico, 80% of the children who died from diarrhoea or acute respiratory infections (ARI) in 1992-1993 received medical care; in more than 70% of cases it was provided by a private general practitioner (GP). The present study evaluated the quality of case management by private and public GPs to children under five years of age with diarrhoea and ARI. During the clinical observation, the treatment and counselling given to the mother were assessed with the WHO guidelines as reference standard. A total of 41 private and 40 public GPs were evaluated for the management of diarrhoea, and 59 private and 40 public GPs for the management of ARI. For diarrhoea, half of the private GPs gave inadequate rehydration therapy, 63% gave incorrect advice on diet, 66% and 49% made an incorrect correct decision in the prescription of antimicrobial and symptomatic drugs, respectively. Public GPs generally performed better in diarrhoea management: 7% gave inadequate rehydration therapy, 13% gave wrong advice on diet, 3% made a wrong decision in the prescription of symptomatic drugs and 28% gave a wrong decision in antimicrobial prescription. In the management of ARI, 66% and 58% of private GPs made a wrong decision in the prescription of antimicrobial and symptomatic drugs, respectively, compared to 30% and 20% of public GPs, respectively. Counselling to the mother given by both private and public GPs was considered inadequate in most cases of diarrhoea and ARI. These results clearly show that private doctors, as important providers of medical care, need to be included in the strategies to improve the quality of care of children with diarrhoea and ARI. Future research needs to address the determinants of the clinical practice of private doctors in countries like Mexico. [ABSTRACT FROM AUTHOR]

Published
1998

169. Study of phenothiazine and <TOGGLE>N</TOGGLE>-methyl phenothiazine by infrared, raman, <SUP>1</SUP>H-, and <SUP>13</SUP>C-NMR spectroscopies

Author

Palafox, M. Alcolea, Gil, M., Núñez, J. L., and Tardajos, G.

Abstract

A complete vibrational analysis of the Fourier transform (FT) infrared (IR) and FT-Raman spectra of both molecules was carried out using quantum chemical calculations. The structure of phenothiazine (PTZ) and N-methylphenothiazine (N-MePTZ) were studied by semiempirical, and ab initio methods. Different basis sets and two new procedures for scaling the frequencies of the ring modes were used. Vibrational data of the methyl group in N-MePTZ were interpreted in terms of the different molecular conformations in the solid state. The 1H- and 13C–nuclear magnetic resonance (NMR) data were interpreted in terms of the electron densities on the atoms and the stacking solute–solute association in dimethyl sulfoxide solution. Chemical shifts were related to the Merz-Kollman atomic charges. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002

Published
2002
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171. Fourier transform Raman spectrum and <TOGGLE>ab initio</TOGGLE> and density functional computations of the vibrational spectrum, molecular geometry, atomic charges and some molecular properties of the anticarcinogenic drug 5-fluorouracil

Author

Rastogi, V. K., Jain, Vaibhav, Yadav, R. A., Singh, Chatar, and Palafox, M. Alcolea

Abstract

FT Raman study of 5-fluorouracil, an anticarcinogenic drug, was carried out. Ab initio and density functional computations of the vibrational spectrum, the molecular geometry, the atomic charges, the total energy, the zero point energy, the rotational constants, the room temperature entropy, (translational, rotational and vibrational) and dipole moment were carried out. The observed Raman wavenumbers were analysed in light of the computed vibrational spectrum. Thermodynamic functions, namely, the enthalpy, the entropy, the heat capacity and the free energy were also computed in the temperature range 200–1000 K using the rigid-rotor harmonic oscillator approximation. For this purpose the fundamental wavenumbers were taken from the present FT-Raman spectrum and the structural parameters were taken from the present theoretically computed geometry. Copyright © 2000 John Wiley & Sons, Ltd.

Published
2000

172. RELIABILITY FACTORS FOR THE MEASUREMENT OF HEPATIC STEATOSIS BY MEANS OF A CONTROLLED ATTENUATION PARAMETER BY TRANSIENT ELASTOGRAPHY

Author

Palafox, M. Figueroa, Juárez-Hernández, E., and Lopez-Mendéz, Y.I.

Abstract

The controlled attenuation parameter (CAP) allows the indirect measurement of liver fat and the indirect the indirect measurement of liver fat and stiffness by transient elastography. Its diagnostic utility has been validated, but the factors for its reliability are unknown. Therefore, the objective is to evaluate the predictors of CAP quality by transient elastography.

Published
2022
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174. “South to North increasing gradient of paternal European ancestry throughout the Mexican territory: Evidence of Y-linked short tandem repeats”.

Author

Rangel-Villalobos, H., Salazar-Flores, J., Dondiego, R., Anaya-Palafox, M., Nuño-Arana, I., Canseco-Ávila, L.M., Flores-Flores, G., Romero-Rentería, O., Morales-Vallejo, M.E., Muñoz-Valle, J.F., and Rubi-Castellanos, R.

Subjects
REPEATED sequence (Genetics), GENEALOGY, Y chromosome, DATABASES, DNA fingerprinting, MESTIZOS, EUROPEANS
Abstract

Abstract: We genotyped at least 12 Y-STRs in DNA samples of 986 Mestizos from five states: Aguascalientes (n =293), Jalisco (n =185), Guanajuato (n =168), Chiapas (n =170), and Yucatán (n =170). Powerplex-Y and AmpFℓSTR® Y-filer® kits were employed, offering a minimum haplotype diversity of 99.69% and 99.88%, respectively. The inclusion of additional Y-STR databases to the analyses allowed obtaining a Y-STR variability landscape from Mexico. Genetic relatedness and preliminary admixture estimates confirmed a population differentiation gradient throughout the Mexican territory: the European ancestry increments to the Northwest and, correspondingly, the Amerindian ancestry increments to the Southeast. These results must be considered for human identification purposes given that most states in Mexico do not have a proper Y-STR database. [Copyright &y& Elsevier]

Published
2009
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175. Contributory presentations/posters

Author

Manoj, N., Srinivas, V., Surolia, A., Vijayan, M., Suguna, K., Ravishankar, R., Suguna, K., Surolia, A., Vijayan, M., Schwarzenbacher, R., Zeth, K., Diederichs, Kostner, G., Gries, A., Laggner, P., Prassl, R., Madhusudan, Akamine, Pearl, Xuong, Nguyen-huu, Taylor, Susan, Sagar, M., Ravishankar, R., Saikrishnan, K., Roy, S., Purnapatre, K., Handa, P., Varshney, U., Vijayan, M., Biswal, B., Sukumar, N., Vijayan, M., Rao, J., Johnson, A., Pattabhi, Vasantha, Krishna, S., Sastri, Mira, Savithri, H., Murthy, M., Pillai, Bindu, Kannan, Hosur, M., Kumar, Mukesh, Patwardhan, Swati, Kannan, K., Hosur, M., Padmanabhaa, B., Sasaki-Sugio, S., Nukaga, M., Matsuzaki, T., Karthikevan, S., Sharma, S., Sharma, A., Paramasivam, M., Kumar, P., Khan, J., Yadav, S., Srinivasan, A., Singh, T., Gourinath, S., Alam, Neelima, Srintvasan, A., Singh, T., Chandra, Vikas, Kaur, Punit, Betzel, Ch., Singh, T., Ghosh, S., Bera, A., Bhattacharya, S., Chakraborty, S., Pal, A., Mukhopadhyay, B., Dey, I., Haldar, U., Baneriee, Asok, Sevcik, Jozef, Solovicova, Adriana, Sekar, K., Sundaralingam, M., Betzel, Ch., Genov, N., Singh, T., Liang, Dong-cai, Jiang, Tao, Zhang, Ji-ping, Chang, Wen-rui, Jahnke, Wolfgang, Blommers, Marcel, Panchal, S., Hosur, R., Pillay, Bindu, Hosur, M., Mathur, Puniti, Srivatsun, S., Joshi, Ratan, Jaganathan, N., Chauhan, V., Atreya, H., Sahu, S., Chary, K., Govil, Girjesh, Adjadj, Elisabeth, Quinjou, Éric, Izadi-Pruneyre, Nadia, Blouquit, Yves, Mispelter, Joël, Heyd, Bernadette, Lerat, Guilhem, Milnard, Philippe, Desmadreil, Michel, Lin, Y., Rao, B., Raghunathan, Vidva, Chau, Mei, Rao, B., Pesais, Prashant, Srivastava, Sudha, Coutinho, Evans, Saran, Anil, Sapico, Leizl, Gesme, Jayson, Lijima, Herbert, Paxton, Raymond, Srikrishnan, Thamarapu, Grace, C., Nagenagowda, G., Lynn, A., Cowsik, Sudha, Sahu, Sarata, Chauhan, S., Bhattacharya, A., Chary, K., Govil, G., Kumar, Anil, Pellecchia, Maurizio, Zuiderweg, Erik, Kawano, Keiichi, Aizawa, Tomoyasu, Fujitani, Naoki, Hayakawa, Yoichi, Ohnishi, Atsushi, Ohkubo, Tadayasu, Kumaki, Yasuhiro, Hikichi, Kunio, Nitta, Katsutoshi, Rani Parvathy, V., Chary, K., Kini, R., Govil, G., Koshiba, Takumi, Kobashigawa, Yoshihiro, Yao, Min, Demura, Makoto, Nakagawa, Astushi, Tanaka, Isao, Kuwajima, Kunihiro, Nitta, Katsutoshi, Linge, Jens, Donoghue, Seán, Nilges, Michael, Chakshusmathi, G., Ratnaparkhi, Girish, Madhu, P., Varadarajan, R., Tetreau, C., Tourbez, M., Lavalette, D., Manno, M., Biagio, P., Martorana, V., Emanuele, A., Vaiana, S., Bulone, D., Palma-Vittorelli, M., Palma, M., Trivedi, V., Cheng, S., Chien, W., Yang, S., Francis, S., Chang, D., Batra, Renn, Geeves, Michael, Manstein, Dietmar, Trvlska, Joanna, Grochowski, Pawel, Geller, Maciej, Ginalski, K., Grochowski, P., Lesyng, B., Lavalette, P., Tetreau, C., Tourbez, M., Blouquit, Y., Roccatano, D., Amadei, A., Nola, A., Berendsen, H., Ho, Bosco, Curmi, P., Berry, H., Lairez, D., Pauthe, E., Pelta, J., Kothekar, V., Sahi, Shakti, Srinivasan, M., Singh, Anil, Madhusudnan, Kartha, Nandel, Fateh, Kaur, Harpreet, Nandel, Fateh, Singh, Balwinder, Jain, D., Feenstra, K., Berendsen, Herman, Tama, F., Sanejouand, Y., Go, N., Sharma, Deepak, Sharma, Sunita, Pasha, Santosh, Brahmachari, Samir, Viiavaraghavan, R., Makker, Jyoti, Dey, Sharmisllia, Kumar, S., Singh, T., Lakshmikanth, G., Krishnamoorthy, G., Mazhul, V., Zaitseva, E., Kierdaszuk, Borys, Widengren, J., Terry, B., Mets, Ü., Rigler, R., Swaminathan, R., Thamotharan, S., Yathindra, N., Shibata, Y., Chosrowjan, H., Mataga, N., Morisima, I., Chakraharty, Tania, Xiao, Ming, Cooke, Roger, Selvin, Paul, Branca, C., Faraone, A., Magazù, S., Maisano, G., Migliardo, P., Villari, V., Behere, Digambar, Deva, M., Brunori, M., Cutruzzolà, F., Gibson, Q., Savino, C., Travaglini-Allocatelli, C., Vallone, B., Prasad, Swati, Mazumdar, Shyamalava, Mitra, Samaresh, Soto, P., Fayad, R., Sukovataya, I., Tyulkova, N., Mamedov, Sh., Aktas, B., Canturk, M., Aksakal, B., Yilgin, R., Bogutska, K., Miroshnichenko, N., Chacko, S., DiSanto, M., Hypolite, J., Zheng, Y-M., Wein, A., Wojciechowski, M., Grycuk, T., Antosiewicz, J., Lesyng, B., Ceruso, Marc, Nola, Alfredo, Bandvopadhvay, Subhasis, Chatterjee, Bishnu, Choudhury, Devapriva, Thompson, Andrew, Stojanoff, Vivian, Pinkner, Jerome, Hultgren, Scott, Khight, Stefan, Flatters, Delphine, Goodfellow, Julia, Takazawatt, Fumi, Kanehisa, Minoru, Sasai, Masaki, Nakamura, Hironori, Sasai, Masaki, Han, Wang, Zheng, Yuan, Xin, Wang, Min, Pan, Bhakuni, Vlnod, Kulkarni, Sangeeta, Ahmad, Atta, Prakash, Koodathingal, Prajapati, Shashi, Surin, Alexey, Matsumoto, Tomoharu, Yang, Li, Nakagawa, Yuki, Kimura, Kazumoto, Amemiya, Yoshiyuki, Semisotnov, Gennady, Kihara, Hiroshi, Tayyab, Saad, Muzammil, Salman, Kumar, Yogesh, Kulkarni, Sangeeta, Prajapati, Shashi, Prakash, Koodathingal, Ahmad, Atta, Bhakuni, Vinod, Sundd, Monica, Kundu, Suman, Jagannadham, M., Kundu, Suman, Sundd, Monica, Jagannadham, Medicherla, Chandani, Bina, Dhar, Ruby, Sinha, Lalankumar, Warrier, Deepti, Mehrotra, Sonam, Khandelwal, Purnima, Seth, Subhendu, Hosur, R., Sasidhar, Y., Prabha, C., Gidwani, Arun, Ahmad, Atta, Kulkarni, Sangeeta, Madhusudan, K., Bhakuni, Vinod, Kinjo, Akira, Nishikawa, Ken, Chakravarty, Suvobrata, Varadarajan, Raghavan, Noyelle, K., Haezebrouck, P., Joniau, M., Dael, H., Dash, Sheffali, Jha, Indra, Bhat, Rajiv, Mohanty, Prasanna, Bandyopadhyay, A., Sonawat, H., Rao, Ch., Datta, Siddhartha, Rajaraman, K., Raman, B., Ramakrishna, T., Rao, Ch., Pande, A., Pande, J., Betts, S., Asherie, N., Ogun, O., King, J., Benedek, G., Sokolova, I., Tyulkova, N., Kalacheva, G., Sonoyama, Masashi, Yokoyama, Yasunori, Taira, Kunihiro, Mitaku, Shigeki, Nakazawal, Chicko, Sasakil, Takanori, Mukai, Yuri, Kamo, Naoki, Sonoyama, Masashi, Mitaku, Shigeki, Dalal, Seema, Regan, Lynne, Mukai, Yuri, Kamo, Naoki, Mituku, Shigeki, Roychoudhury, Mihir, Kumar, Devesh, Lőrinczv, Dénes, Könczöl, Franciska, Farkas, László, Belagyi, Joseph, Schick, Christoph, Thomson, Christy, Ananthanarayanan, Vettai, Alirzayeva, E., Baba-Zade, S., Gromiha, M., Oobatake, M., Kono, H., An, J., Uedaira, H., Sarai, A., Takano, Kazufumi, Yamagata, Yuriko, Yutani, Katsuhide, Jas, Gouri, Muñoz, Victor, Hofrichter, James, Eaton, William, Penoyar, Jonathan, Srikrishnan, Thamarapu, Lo Verde, Philip, Kardos, J., Bódi, Á., Venekei, I., Závodszky, P., Gráf, L., Szilágyi, András, Závodszky, Péter, Allan, R., Walshaw, J., Woolfson, D., Funahashi, Jun, Takano, Kazufumi, Yamagata, Yuriko, Yutani, Katsuhide, Gupta, Savan, Mazumdar, Shyamalava, Di Nola, A., Mangoni, M., Roccatano, P., Ramachandraiah, Gosu, Chandra, Nagasuma, Kothekar, V., Srinivasan, M., Sahi, Shakti, Chakraborty, S., Bhattacharya, S., Bera, A., Ghosh, S., Pal, A., Haldar, U., Mukhopadhyay, B., Baneriee, Asok, Ciani, Barbara, Woolfson, Derek, Nair, Usha, Kaur, Kanwal, Salunke, Dinakar, Swaminathan, Chittoor, Surolia, Avadhesha, Rigler, R., Pramanik, A., Jonasson, P., Kratz, G., Jansson, O., Nygren, P., Ståhl, S., Ekberg, K., Johansson, B., Uhlén, S., Uhlén, M., Jörnvall, H., Wahren, J., Welfle, Karin, Misselwitz, Rolf, Höhne, Wolfgang, Welfle, Heinz, Mazhul, V., Zaitseva, E., Mitskevich, L., Fedurkina, N., Kurganov, B., Jarori, Gotam, Maity, Haripada, Guharay, J., Sengupta, B., Sengupta, P., Sridevi, K., Kasturi, S., Gupta, S., Agarwal, Gunjan, Kwong, Suzanne, Briehl, Robin, Ismailova, O., N, Tyulkova, Hariharan, C., Pines, D., Pines, E., Zamai, M., Cohen-Luria, R., Yayon, A., Parola, A., Padya, M., Spooner, G., Woolfeon, D., Bakshi, Panchan, Sharma, Deepak, Sharma, Sunita, Bharadwaj, D., Pasha, Santosh, Sharma, U., Srivastava, N., Barthwal, R., Jagannathan, N., Matsuda, Keiko, Nishioka, Takaaki, Go, Nobuhiro, Aita, T., Urata, S., Husimi, Y., Majumder, Mainak, Chatterjee, Bishnu, Abrescia, Nicola, Malinina, Lucy, Subirana, Juan, Aymami, Juan, Eritxa, Ramón, Coll, Miquel, Premraj, B., Yathindra, N., Thenmalarchelvi, R., Yathindra, N., Kumar, P., Gautham, N., Kan, Lou, Ming-Hou, Lin, Shwu-Bin, Sana, Tapas, Roy, Kanal, Bruant, N., Flatters, D., Lavery, R., Genest, D., Rons, Remo, Sklenar, Heinz, Lavery, Richard, Kundu, Sudip, Bhattacharyya, Dhananjay, Bandyopadhyay, Debashree, Thakur, Ashoke, Majumdar, Rabi, Barceló, F., Portugal, J., Ramanathan, Sunita, Chary, K., Rao, B., Gliosli, Mahua, Kumar, N., Varshney, Umesh, Chary, K., Pataskar, Shashank, Brahmachari, Samir, Sarojini, R., Selvasekarapandian, S., Kolandaivel, P., Sukumar, S., Selvasekarapandian, S., Sarojini, R., Kolmdaivel, P., Sukumar, S., Sarojini, R., Selvasekarapandian, S., Kolandaivel, P., Sukumar, S., Selvasekarapandian, S., Sarojini, R., Kolandaivel, P., Sukumar, S., Maiti, Motilal, Sen, Anjana, Das, Suman, Terra, Elisa, Suraci, Chiara, Diviacco, Silvia, Quadrifoglio, Franco, Xodo, Luigi, Bandyopadhyay, Debashree, Bhattacharyya, Dhananjay, Kundu, Sudip, Thakur, Ashoke, Das, Suman, Ray, Arghya, Maiti, Motilal, Karthikeyan, G., Chary, Kandala, Rao, Basuthkar, Mujeeb, Anwer, James, Thomas, Kasyanenko, N., Haya, E., Bogdanov, 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F., Tahradník, Ivan, Pavelková, Jana, Zahradniková, Alexandra, Zhorov, Boris, Ananthanaravanan, Vettai, Michailov, M., Neu, E., Seidenbusch, W., Gornik, E., Martin, D., Welscher, U., Weiss, D., Pattnaik, B., Jellali, A., Forster, V., Hicks, D., Sahel, J., Dreyfus, H., Picaud, S., Wang, Hong-Wei, Sui, Sen-fang, Luther, Pradeep, Barry, John, Morris, Ed, Squire, John, Sundari, C., Balasubramanian, D., Veluraia, K., Christlet, T., Suresh, M., Berry, H., Pelta, J., Lairez, D., Laretta-Garde, V., Krilov, Dubravka, Stojanović, Nataša, Herak, Janko, Jasuja, Ravi, Ivanova, Maria, Mirchev, Rossen, Ferrone, Frank, Stopar, David, Spruijt, Ruud, Wolfs, Cor, Hemminga, Marcus, Arcovito, G., Spirito, M., Sui, Sen-fang, Wang, Hong-Wei, Agrawal, Rajendra, Heagle, Amy, Penczek, Pawel, Grassucci, Robert, Frank, Joachim, Sharma, Manjuli, Jeyakumar, Loice, Fleischer, Sidney, Wagenknecht, Terence, Knupp, Carlo, Munro, Peter, Luther, Pradeep, Ezra, Eric, Squire, John, Ichihara, Koji, Kitazawa, Hidefumi, Iguchi, Yusuke, Hotani, Hirokazu, Itoh, Tomohiko, Pifat, Greta, Kveder, Marina, Pečar, Slavko, Schara, Milan, Nair, Deepak, Singh, Kavita, Rao, Kanury, Salunke, Dinakar, Kaur, Kanwaljeet, Jain, Deepti, Sundaravadivel, B., Goel, Manisha, Salunke, D., Kovalenko, E., Semenkova, G., Cherenkevich, S., Lakshmanan, T., Sriram, D., Srinivasan, S., Loganathan, D., Ramalingam, T., Lebrón, J., Bjorkman, P., Singh, A., Gayatri, T., Jain, Deepti, Kaur, Kanwaljeet, Sundaravadivel, B., Salunke, Dinakar, Caffarena, Ernesto, Grigera, J., Bisch, Paulo, Kiessling, V., Fromherz, P., Rao, K., Gaikwad, S., Khan, M., Suresh, C., Kaliannan, P., Gromiha, M., Elanthiraiyan, M., Chadha, K., Payne, J., Ambrus, J., Nair, M., Nair, Madhavan, Mahajan, S., Chadha, K., Hewitt, R., Schwartz, S., Bourguignon, J., Faure, M., Cohen-Addad, C., Neuburger, M., Ober, R., Sieker, L., Macherel, D., Douce, R., Gurumurthy, D., Velmurugan, S., Lobo, Z., Srivastava, Sudha, Phadke, Ratna, Govil, Girjesh, Desai, Prashant, Coutinho, Evans, Guseinova, I., Suleimanov, S., Zulfugarov, I., Novruzova, S., Aliev, J., Ismayilov, M., Savchenko, T., Alieva, D., Ilík, Petr, Kouřil, Roman, Bartošková, Hana, Nauš, Jan, Gaikwad, Jvoti, Thomas, Sarah, Vidyasagar, P., Garab, G., Simidjiev, I., Rajagopal, S., Várkonyi, Zs., Stoylova, S., Cseh, Z., Papp, E., Mustárdy, L., Holzenburg, A., Bruder, R., Genick, U., Woo, T., Millar, D., Gerwert, K., Getzoff, E., Jávorfí, Tamás, Garab, Győző, Naqvi, K., Kalimullah, Md., Gaikwad, Jyoti, Thomas, Sarah, Semwal, Manoj, Vidyasagar, P., Kouril, Roman, Ilik, Petr, Naus, Man, Pomozi, István, Horváth, Gábor, Wehner, Rüdiger, Bernard, Gary, Damjanović, Ana, Ritz, Thorsten, Schulten, Klaus, Jushuo, Wang, Jixiu, Shan, Yandao, Gong, Tingyun, Kuang, Nanming, Zhao, Freiberg, Arvi, Timpmann, Kõu, Ruus, Rein, Woodbury, Neal, Nemtseva, E., Kudryasheva, N., Sizykh, A., Shikhov, V., Nesterenko, T., Tikhomirov, A., Forti, Giorgio, Finazzi, Giovanni, Furia, Alberto, Barbagallo, Romina, Forti, Giorgio, Iskenderova, S., Agalarov, R., Gasanov, R., Osamu, Miyashita, Nobuhiro, G., Soni, R., Ramrakhiani, M., Yagi, Hiromasa, Tozawa, Kacko, Sekino, Nobuaki, Iwabuchi, Tomoyuki, Yoshida, Masasuke, Akutsu, Hideo, Avetisyan, A., Kaulen, A., Skulachev, V., Feniouk, B., Breyton, Cécile, Kühlbrandt, Werner, Assarsson, Maria, Gräslund, Astrid, Zsiros, O., Horváth, G., Mustárdy, L., Libisch, B., Gombos, Z., Budagovskaya, N., Kudryasheva, N., Harada, Erisa, Fukuoka, Yuki, Ohmura, Tomoaki, Fukunishi, Arima, Kawai, Gota, Watanabe, Kimitsuna, Akutsu, Hideo, Derganc, Jure, Božič, Bojan, Svetina, Saša, Žekš, Boštjan, Hoh, J., Li, Z., Rossmanith, G., Beer, E., Treijtel, B., Frederix, P., Blangè, T., Hénon, S., Galtet, F., Laurent, V., Planus, E., Isabey, D., Rath, L., Dash, P., Raval, M., Ramakrishnan, C., Balaram, R., Randic, Milan, Basak, Subhash, Vracko, Marjan, Nandy, Ashesh, Amic, Dragan, Beslo, Drago, Nikolic, Sonja, Trinajstic, Nenad, Walahaw, J., Woolfson, D., Lensink, Marc, Berendsen, Herman, Reddy, Boojala, Shindylov, Ilya, Bourne, Philip, Donnamaria, M., Xammar Oro, J., Grigera, J., Neagu, Monica, Neagu, Adrian, Praprotnik, Matej, Janežič, Dušanka, Mark, Pekka, Nilsson, Lennart, Martorana, V., Bulone, D., Fata, L., Manno, M., Biagio, P., Dardenne, Laurent, Werneck, Araken, Neto, Marçal, Bisch, Paulo, Kannan, N., Vishveshwara, S., Christlet, T., Veluraja, K., Grunwald, Gregory, Balaban, Alexandra, Basak, Kanika, Gute, Brian, Mills, Denise, Opitz, David, Balasubramanian, Krishnan, Mihalas, G., Lungeanu, Diana, Macovievici, G., Gruia, Raluca, Neagu, Monica, Cortez-Maghelly, C., Dalcin, B., Passos, E., Blesic, S., Ljubisavljevic, M., Milosevic, S., Stratimirovic, D., Bachhawat, Nandita, Mande, Shekhar, Ghosh, S., Nandy, A., Saito, Ayumu, Nishigaki, Koichi, Nishigaki, Koichi, Naimuddin, Mohammed, Mitaku, Shigeki, Hirokawa, Takatsugu, Ono, Mitsuo, Takaesu, Hirotomo, El Gohary, M., Ahmed, Abdalla, Eissa, A., Nakashima, Hiroshi, Nishikawa, Ken, Neagu, Monica, Neagu, Adrian, 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A., Macpherson, J., O’Hare, D., Winlove, C., Unwin, P., Sengupta, P., Phillip, R., Banerjee, S., Kumar, G., Maiti, S., Nagayaka, K., Danev, R., Sugitani, S., Murata, K., Gősch, Michael, Blom, H., Thyberg, P., Földes-Papp, Z., Björk, G., Holm, J., Heino, T., Rigler, Rudolf, Yokochi, Masashi, Inagaki, Fuyuhiko, Kusunoki, Masami, Matthews, E., Pines, J., Chukova, Yu., Koltover, Vitaly, Bansal, Geetanjali, Singh, Uma, Bansal, M., Nakata, Kotoko, Nakano, Tastuya, Kaminuma, Tsuguchika, Kang, B., Singh, U., Kirn, Bonn, Potocnik, Neja, Stare, Vito, Shukla, Latal, Natarajan, V., Devasagayam, T., Sastry, M., Kesavan, P., Sayfutdinov, R., Adamovich, V., Rogozin, D., Degermendzhy, A., Khetrapal, C., Ramanathan, K., Gowda, G., Ghimire, Kedar, Masaru, Ishida, Fujita, H., Ishiwata, S., Kishimoto, Y., Kawahara, S., Suzuki, M., Mori, H., Mishina, M., Kirino, Y., Ohshima, H., Dukhin, A., Shilov, V., Goetz, P., Sengupta, B., Guharay, J., Sengupta, P., and Mishra, R.

Published
1999
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176. Scaling Factors for the Prediction of the Frequencies of the Ring Modes in Benzene Derivatives

Author

Palafox, M. A.

Abstract

The performance of semiempirical, ab initio, and density functional methods in calculating and describing the vibrational frequencies of benzene and several derivatives was determined. Different levels were used. The normal modes of the ring were characterized by the magnitude and direction of the displacement vector. Two new procedures of scaling the frequencies were presented. Scaling factors were determined at different levels. A significant reduction in the predicted frequencies of the ring modes of several benzene derivatives was obtained over the one-factor overall scaling procedure.

Published
1999

177. Classical and Inverted Structures of SiX<INF>n</INF><INF></INF>H<INF>3</INF><INF>-</INF><INF>n</INF><INF></INF>Li and SiX<INF>n</INF><INF></INF>H<INF>3</INF><INF>-</INF><INF>n</INF><INF></INF>Na

Author

Gomez, P. C., Palafox, M. A., and Pacios, L. F.

Abstract

Geometry, energetics, and dipole moments of tetrahedral-like (classical) and inverted forms of SiXnH3-nLi and SiXnH3-nNa, where X stands for a halogen atom, are studied ab initio at HF, MP2, QCISD(T), and B3LYP levels of the theory using triple-ζ plus polarization and diffuse functions basis sets. The inverted form is found to be the most stable for all the cases where Li is present but not in all the cases involving Na. Energy differences between classical and inverted forms range from −2 to 24 kcal mol-1. The results for SiH3Li agree with previous data. Agreement of the properties determined using this methodology with the experimental results, where available, is found very satisfactory. An analysis of the bonding in these molecules in terms of atomic charges and electron density is carried out.

Published
1999

179. Comparison Between the IR Spectra and the Structure of the Two Conformations of a Diazabicyclanol

Author

Palafox, M. Alcolea

Abstract

In the two stable conformations of the diazabicyclanol 3, 7-dimethyl-3, 7-diazabicyclo[3. 3. 1]nonan-9-ol, chair-chair (Va) and chair-boat (Vb), the infrared spectra (200-4000 cm-1) were recorded, compared and their vibrations analysed. Using the AMI senlempirical method, the geometry was fully optimized in both forms, and the theoretical Infrared spectra were calculated and compared. In the (Vb) conformation, the IR spectra were recorded in CCl3D, CCl4 and S2C solvents. Some correlations were established.

Published
1994
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184. The impact of a clinical training unit on integrated child health care in Mexico

Author

Guiscafré Héctor, Martínez Homero, Palafox Miguel, Villa Sofía, Espinosa Patricia, Bojalil Rossana, and Gutiérrez Gonzalo

Subjects
Delivery of health care, Integrated, Pediatrics/education, Clinical medicine/education, Hospitals, Teaching, Models, Educational, Mexico, Public aspects of medicine, RA1-1270
Abstract

This study had two aims: to describe the activities of a clinical training unit set up for the integrated management of sick children, and to evaluate the impact of the unit after its first four years of operation. The training unit was set up in the outpatient ward of a government hospital and was staffed by a paediatrician, a family medicine physician, two nurses and a nutritionist. The staff kept a computerized database for all patients seen and they were supervised once a month. During the first three years, the demand for first-time medical consultation increased by 477% for acute respiratory infections (ARI) and 134% for acute diarrhoea (AD), with an average annual increase of demand for medical care of 125%. Eighty-nine per cent of mothers who took their child for consultation and 85% of mothers who lived in the catchment area and had a deceased child received training on how to recognize alarming signs in a sick child. Fifty-eight per cent of these mothers were evaluated as being properly trained. Eighty-five per cent of primary care physicians who worked for government institutions (n = 350) and 45% of private physicians (n = 90) were also trained in the recognition and proper management of AD and ARI. ARI mortality in children under 1 year of age in the catchment area (which included about 25 000 children under 5 years of age) decreased by 43.2% in three years, while mortality in children under 5 years of age decreased by 38.8%. The corresponding figures for AD mortality reduction were 36.3% and 33.6%. In this same period, 11 clinical research protocols were written. In summary, we learned that a clinical training unit for integrated child care management was an excellent way to offer in-service training for primary health care physicians.

Published
2001

185. The role of the muscarinic system in regulating estradiol secretion varies during the estrous cycle: the hemiovariectomized rat model

Author

Rodríguez Jorge O, Meléndez Griselda, Palafox María T, Flores Angélica, Cruz María E, Chavira Roberto, and Domínguez Roberto

Subjects
Gynecology and obstetrics, RG1-991, Reproduction, QH471-489
Abstract

Abstract There is evidence that one gonad has functional predominance. The present study analyzed the acute effects of unilateral ovariectomy (ULO) and blocking the cholinergic system, by injecting atropine sulfate (ATR), on estradiol (E2) serum concentrations during the estrous cycle. The results indicate that ULO effects on E2 concentrations are asymmetric, vary during the estrous cycle, and partially depend on the cholinergic innervation. Perforation of the left peritoneum resulted in lower E2 serum concentrations in the three stages of the estrous cycle. At proestrus, unilateral or bilateral perforation of the peritoneum resulted in lower E2 serum concentrations. ULO of the right ovary (left ovary in situ) resulted in significantly higher E2 concentrations than animals with ULO of the left ovary (right ovary in situ). ATR treatment to ULO rats on D1 resulted in a significant drop of E2 serum concentrations. ULO rats treated with ATR on D2 or P, resulted in an asymmetrical E2 secretion response; when the right ovary remained in situ an increase in E2 was observed, and a decrease when the left ovary remained in situ. The results obtained in the present study suggest that each ovary's ability to compensate the secretion of E2 from the missing ovary is different and varies during the estrous cycle. The results also suggest that the cholinergic system participates in regulating ovarian E2 secretion. Such participation varies according to the ovary remaining in situ and the stage of the estrous cycle of the animal. The results agree with previously stated hypothesis of a neural pathway arising from the peritoneum that participates in regulating E2 secretion, and also supports the idea of cross-talk between the ovaries, via a neural communication, that modulates E2 secretion.

Published
2006
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186. The acute asymmetric effects of hemiovariectomy on testosterone secretion vary along the estrous cycle. The participation of the cholinergic system

Author

Chavira Roberto, Barco Ana I, Meléndez Griselda, Palafox María T, Rodríguez Jorge O, Flores Angélica, Esther Cruz M, and Domínguez Roberto

Subjects
Gynecology and obstetrics, RG1-991, Reproduction, QH471-489
Abstract

Abstract The presence of asymmetry in the capacity of the left and right ovaries to secrete testosterone was analyzed by studying the effects of hemiovariectomy along the estrus cycle one hour after surgery. The effects of ether anesthesia on hormone serum levels were also analyzed. Bilateral ovariectomy and the extirpation of the left ovary performed on the day of proestrus resulted in significantly lower testosterone levels. Compared to the anesthetized group, the effects of perforating the peritoneum unilaterally varied according to the day of the estrous cycle and the side of the peritoneum surgery was performed on. Injecting atropine sulfate (ATR) to control or anesthetized rats on D1 resulted in a significant increase of testosterone serum levels. The effects of perforating the peritoneum on testosterone levels depended on the cholinergic innervation and varied along the estrous cycle. Blocking the cholinergic system before performing unilateral or bilateral ovariectomy had different effects depending on the day of the estrous cycle. Testosterone plasma levels increased significantly when surgery was performed on the day of diestrus and dropped when surgery was performed on proestrus. Similar effects were observed when the left adrenal was extirpated from animals with the cholinergic system blocked. The results presented herein support the hypothesis of asymmetry in the ovaries' abilities to secrete steroid hormones, and that the capacity to secrete testosterone varies along the estrous cycle.

Published
2006
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188. A structural, magnetic and colloidal stability study of uncoated and silica coated iron oxide samples prepared in two different surfactants.

Author

Hernán, E., Isasi, J., Rapp, M., Palafox, M. Alcolea, and Marco, J.F.

Subjects
*FOURIER transform infrared spectroscopy, *FERRIC oxide, *MAGNETIC materials, *MOSSBAUER spectroscopy, *TRANSMISSION electron microscopy
Abstract

The discovery of new magnetic materials of interest in the biomedicine field is a relevant topic in current research. For years, our research group has been investigating the obtaining and study of nanostructured magnetic samples that behave superparamagnetically to enable their transport in living organisms. We present here a study that summarizes the structural characteristics, magnetic behavior and stability of two Fe 3 O 4 samples synthesized by coprecipitation that were dispersed using two different surfactants (oleylamine, OL, and oleic acid, OA), and two others prepared from the previous ones by reaction with tetraethyl orthosilicate (TEOS). The relationships between the surfactant used in the synthesis, the presence of a certain maghemite (γ-Fe 2 O 3) content, the influence of silica shell thickness and magnetic behaviour of all samples were systematically studied by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), Mössbauer spectroscopy and H vs. M loops. Rietveld refinements of the XRD profiles confirmed a partial oxidation of the non-silica-coated samples and FTIR spectra of the uncoated samples showed a very strong broad metal-oxygen band and additional sets of bands from the different organic chains of the two surfactants. Individual particles with a mean diameter of 7 and 9 nm were distinguished in TEM images of uncoated magnetic samples. Mössbauer data indicated the presence of non-stoichiometric magnetite in all samples, in agreement with XRD refinements. Magnetic measurements confirmed the superparamagnetic behavior of all the samples. Highest negative zeta potential values are found for the silica covered samples in both acidic and basic medium, being Fe 3 O 4 -AO@SiO 2 the best suited for the purposes of its dispersibility in future applications. Low polydispersity index (PDI) values confirmed the best stability and dispersibility of all samples investigated in tetrahydrofuran (THF). [Display omitted] • Fe 3 O 4 -OL, Fe 3 O 4 -OA, Fe 3 O 4 -OL @SiO 2 , Fe 3 O 4 -OA @SiO 2 samples were synthesized via coprecipitation with oleylamine or oleic acid, followed by TEOS reaction. • TEM images revealed spherical particles with diameters of 7 nm (Fe 3 O 4 -OL) and 9 nm (Fe 3 O 4 -AO), and elongated silica-coated pockets containing nanoparticles (16–19 nm). • Mössbauer and magnetic measurements confirmed non-stoichiometric magnetite having different stoichiometry degrees and the superparamagnetic behavior. • All samples exhibited higher negative zeta potential and lower PDI, indicating better dispersibility in H 2 O and THF. [ABSTRACT FROM AUTHOR]

Published
2024
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190. FT-IR and FT-Raman spectra of 6-chlorouracil: Molecular structure, tautomerism and solid state simulation. A comparison between 5-chlorouracil and 6-chlorouracil.

Author

Ortiz, S., Alvarez-Ros, M.C., Alcolea Palafox, M., Rastogi, V.K., Balachandran, V., and Rathor, S.K.

Subjects
*FOURIER transform infrared spectroscopy, *RAMAN spectra, *MOLECULAR structure, *TAUTOMERISM, *SOLID state chemistry, *HALOGENATION
Abstract

Highlights: [•] All the tautomers of 6-chlorouracil are more stable than those in uracil molecule. [•] The Raman and IR spectra of 6-ClU in the solid state were simulated and interpreted. [•] The solid state simulation with scaled values was carried out by a tetramer form. [•] Halogenation produces a smaller effect for 5-XU than for 6-XU derivatives. [•] The low energy gap HOMO–LUMO facilitates the intra molecular charge transfer. [Copyright &y& Elsevier]

Published
2014
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191. Seasonal chlorophyll fluorescence before and after rapid light curves in the endangered species Lophophora diffusa (Cactaceae) across two microenvironments.

Author

González-Salvatierra, Claudia, Flores, Joel, Díaz-Segura, Omar, Matías-Palafox, M. Loraine, and Jiménez-Sierra, Cecilia L.

Subjects
*LIGHT curves, *SPRING, *CHLOROPHYLL spectra, *PLANT photoinhibition, *AUTUMN
Abstract

• L. diffusa plants under direct sunlight suffer dynamic photoinhibition. • Acclimation with NPQ was observed by rapid light curves in exposed cacti in spring. • L. diffusa shows high tolerance to high-light conditions (high PPFD sat values). • PPFD sat values found for L. diffusa are the highest in the cactaceae. In desert environments, intense light stress can significantly impede the growth and survival of plants, making microenvironments formed under nurse plants crucial. Chlorophyll a fluorescence serves as a widely employed tool for detecting plant stress conditions. Here, we investigated the seasonal ecophysiological performance of Lophophora diffusa (Cactaceae) under nurse plants and in direct sunlight. Our assessment involved monitoring chlorophyll fluorescence parameters as indicators of photosynthetic efficiency over the course of one year, including the effective quantum yield of photosystem II (Φ PSII), maximum quantum efficiency of photosystem II (F v /F m), electron transport rate (ETR), and non-photochemical quenching (NPQ). Higher daily PPFD levels were observed in open spaces throughout all seasons except for winter. Additionally, temperatures were lower beneath nurse plants compared to exposed sites during spring and autumn. Lophophora diffusa exhibited dynamic photoinhibition, as evidenced by lower F v / F m values in plants exposed to sunlight compared to those sheltered under nurse plants in spring. During rapid light curves, L. diffusa exhibited decreased maximum Φ PSII and maximum ETR values in winter across both microenvironments, while displaying higher maximum NPQ in cacti exposed to sunlight compared to those sheltered under nurse plants in spring. High saturating light levels for ETR were observed in both environments throughout most seasons, except for winter, indicating a high tolerance to high-light conditions. Light curves induced greater stress compared to natural conditions, as evidenced by the acclimation with increased NPQ observed only after rapid light curves. These findings suggest that adult individuals of L. diffusa may not strictly rely on nurse plants for survival and have developed various mechanisms to thrive in diverse microenvironments. [ABSTRACT FROM AUTHOR]

Published
2024
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192. Synthesis, structural and morphological characterization and photoluminescence study of Y0.9Er0.1−xYbxVO4 materials.

Author

Rapp, M., Isasi, J., Alcolea Palafox, M., Muñoz-Ortiz, T., and Ortiz-Rivero, E.

Subjects
*PHOTOLUMINESCENCE, *COATING processes, *HYDROTHERMAL synthesis, *TRANSMISSION electron microscopy, *ERBIUM compounds, *SYMMETRY groups
Abstract

• Y 0.9 Er 0. 1−x Yb x VO 4 samples with x = 0, 0.01, 0.05 and 0.09 were synthesized and coated. • Substitution of Er by Yb leads to up-conversion emission with green and red bands. • Up-conversion emission intensity increases in co-doped samples with the laser power. • Er doped samples exhibit bright green down-conversion emission under stimulation. • Y 0.9 Er 0.09 Yb 0. 01 VO 4 has the highest sensitivity for use as fluorescent nanothermometer. [Display omitted] Erbium/ytterbium-dopped Y 0.9 Er 0. 1−x Yb x VO 4 samples with x = 0, 0.01, 0.05 and 0.09 were synthesized by hydrothermal synthesis at basic pH with urea addition. For comparison purposes, another sample with x = 0 was also prepared by the solgel method. X-ray diffraction patterns were indexed on the basis to a tetragonal symmetry of space group I4 1 /amd with Z = 4 compatible with a zircon-type, in good agreement with FTIR spectra. Additionally, some of the samples were coated with silica, and the successful coating process was verified in both X-ray diffraction profiles and FTIR spectra. Particles of two different morphologies were found in transmission electron microscopy images of uncoated samples, some spherical with sizes between 14 and 20 nm and others elongated. A shell of ~ 5 nm thickness was also observed in silica covered samples. The relationship between dopant content and the luminescence emission was systematically explored. Erbium-doped samples exhibit bright green fluorescence under stimulation at 360 nm. The substitution of erbium by ytterbium successfully produced an up-conversion emission under stimulation at 808 nm, being able to observe green and red emission bands. The potential use as fluorescent thermometers of erbium/ytterbium doped samples at 300, 325 and 350 K was finally investigated. [ABSTRACT FROM AUTHOR]

Published
2022
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194. Comparative structural, morphological and magnetic study of MFe2O4 nanopowders prepared by different synthesis routes.

Author

Arévalo-Cid, P., Isasi, J., Alcolea Palafox, M., and Martín-Hernández, F.

Subjects
*MATERIALS at low temperatures, *PARTICLE size distribution, *MAGNETIC anisotropy, *SUPERPARAMAGNETIC materials, *FERRIMAGNETISM, *HYDROTHERMAL synthesis, *FERRITES
Abstract

• MFe 2 O 4 nanoparticles (M = Fe, Co, Ni) are prepared by three different methods. • Co presence increases the particles size, while Ni decreases it. • Smaller particles are obtained by hydrothermal method. • Fe 3 O 4 presents the lower T B for samples obtained by the same method. • Particle size distribution and magnetic anisotropy are critical factors for T B. M Fe 2 O 4 nanoparticles with M = Fe, Co and Ni were prepared by three different methods (coprecipitation, sol-gel and hydrothermal synthesis). XRD patterns reveal an increase in the unit cell parameter associated to the presence of Fe2+. More intense diffraction maxima are observed for samples prepared by sol-gel. Particle size appears to be larger for Co ferrites and sol-gel samples. By contrast, smaller grain sizes are observed for NiFe 2 O 4 and hydrothermal samples. The highest M s appears in the Fe 3 O 4 obtained by coprecipitation. An increment in the saturation magnetization values is found in the cobalt and nickel samples prepared by hydrothermal method. Iron and nickel samples behave as superparamagnetic materials with low blocking temperatures while CoFe 2 O 4 samples exhibit a characteristic ferrimagnetism. Variations observed in the ZFC/FC curves of coprecipitation-prepared samples are related to both the different particle size distribution and the values of magnetic anisotropy constant. [ABSTRACT FROM AUTHOR]

Published
2020
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195. Targeting mTOR to overcome resistance to hormone and CDK4/6 inhibitors in ER-positive breast cancer models

Author

María Jimena Rodriguez, María Cecilia Perrone, Marina Riggio, Marta Palafox, Valeria Salinas, Andrés Elia, Natali Daiana Salgueiro, Andrea Eugenia Werbach, María Paula Marks, Marcelo A. Kauffman, Luciano Vellón, Violeta Serra, Virginia Novaro, Institut Català de la Salut, [Rodriguez MJ, Perrone MC, Riggio M, Elia A] Instituto de Biología y Medicina Experimental (IBYME-CONICET), Protein Kinases and Cancer Laboratory, Buenos Aires, Argentina. [Palafox M, Serra V] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Salinas V] Hospital JM Ramos Mejía, Neurogenetics Unit, Buenos Aires, Argentina. Universidad Austral, Translational Medicine Research Institute IIMT-CONICET, Buenos Aires, Provincia de Buenos Aires, Argentina, and Vall d'Hebron Barcelona Hospital Campus

Subjects
fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos::resistencia a los antineoplásicos [FENÓMENOS Y PROCESOS], neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance, Neoplasm [PHENOMENA AND PROCESSES], Multidisciplinary, acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas [COMPUESTOS QUÍMICOS Y DROGAS], Otros calificadores::/uso terapéutico [Otros calificadores], Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Other subheadings::/therapy [Other subheadings], Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors [CHEMICALS AND DRUGS], Mama - Càncer - Tractament, Other subheadings::/therapeutic use [Other subheadings], Otros calificadores::/terapia [Otros calificadores], Resistència als medicaments, Proteïnes quinases - Inhibidors - Ús terapèutic
Abstract

Cancer; Cell biology Càncer; Biologia cel·lular Cáncer; Biología celular Resistance to therapy remains a major obstacle in cancer management. Although treatment with hormone and CDK4/6 inhibitors is successful in luminal breast cancer, resistance to these treatments is frequent, highlighting the need for novel therapeutic strategies to delay disease progression and improve patient survival. Here, we assessed the mechanisms of acquired resistance using T47D and MCF-7 tamoxifen- and palbociclib-resistant cell-line variants in culture and as xenografts, and patient-derived cells (PDCs) obtained from sensitive or resistant patient-derived xenografts (PDXs). In these models, we analyzed the effect of specific kinase inhibitors on survival, signaling and cellular aggressiveness. Our results revealed that mTOR inhibition is more effective than PI3K inhibition in overcoming resistance, irrespective of PIK3CA mutation status, by decreasing cell proliferation and tumor growth, as well as reducing cell migration and stemness. Moreover, a combination of mTOR and CDK4/6 inhibitors may prevent pathway reactivation downstream of PI3K, interfering with the survival of resistant cells and consequent tumor escape. In conclusion, we highlight the benefits of incorporating mTOR inhibitors into the current therapy in ER + breast cancer. This alternative therapeutic strategy not only enhances the antitumor response but may also delay the emergence of resistance and tumor recurrence. This work was supported by CONICET, ANPCYT (Grants PICT2509 & PICT0345), Instituto Nacional del Cáncer (Grants 2016 & 2018), Fundación Williams, Fundación Bunge & Born (Oster Grant) (Argentina); Instituto de Salud Carlos III (Grants PI20/00892 & CPII19/0033), Ministerio de Economía y Competitividad (FJCI-2015-25412) (Spain).

Published
2023
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196. High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer

Author

Stefan Michiels, Cristina Saura, Cristina Viaplana, Marta Palafox, Abel Gonzalez-Perez, Alejandra Bruna, Paolo Nuciforo, Marta Guzman, Arribas Joaquín, Meritxell Bellet, Alicia García-Sanz, Violeta Serra, Faye Su, Olga Rodriguez, Nuria Lopez-Bigas, Analia Azaro, Monica Arnedos, Javier Hernández-Losa, Maurizio Scaltriti, Mafalda Oliveira, Laia Monserrat, Marta Capelán, Maria Teresa Herrera-Abreu, Carlos Caldas, Guillermo Villacampa, Leonardo Mina, Judit Grueso, Chandra S. Verma, Srinivasaraghavan Kannan, Robert Clarke, Nusaibah Ibrahimi, R. Dienstmann, Andreu Ódena, Nicholas C. Turner, Fara Brasó-Maristany, Aleix Prat, Mònica Sánchez-Guixé, Kui Lin, Gonzalez-Perez, Abel [0000-0002-8582-4660], Oliveira, Mafalda [0000-0001-9152-8799], Ibrahimi, Nusaibah [0000-0003-4537-0323], Kannan, Srinivasaraghavan [0000-0002-9539-5249], Sánchez-Guixé, Mònica [0000-0002-9430-4413], Hernández, Javier [0000-0003-1526-3201], Clarke, Robert B [0000-0001-5407-3123], Caldas, Carlos [0000-0003-3547-1489], Arribas, Joaquín [0000-0002-0504-0664], Michiels, Stefan [0000-0002-6963-2968], Turner, Nicholas C [0000-0001-8937-0873], Prat, Aleix [0000-0003-2377-540X], Nuciforo, Paolo [0000-0003-1380-0990], Lopez-Bigas, Nuria [0000-0003-4925-8988], Scaltriti, Maurizio [0000-0002-5522-1447], Saura, Cristina [0000-0001-8296-5065], Serra, Violeta [0000-0001-6620-1065], Apollo - University of Cambridge Repository, Institut Català de la Salut, [Palafox M, Monserrat L, Òdena A, Sánchez-Guixé M, Rodríguez O, Guzmán M, Grueso J] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Bellet M, Bellet M, Capelán M, Azaro A, Saura C] Breast Cancer and Melanoma Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Villacampa G, Viaplana C, Dienstmann R] Oncology Data Science Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Gonzalez-Perez A] Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain. Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Spain. [Hernández J] Grup de Recerca de Patologia Molecular Translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Arribas J] CIBERONC, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Growth Factors Laboratory, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. [Nuciforo P] Molecular Oncology Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Serra V] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. CIBERONC, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
endocrine system, Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance, Neoplasm [PHENOMENA AND PROCESSES], endocrine system diseases, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Ubiquitin-Protein Ligases, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], General Physics and Astronomy, Antineoplastic Agents, Breast Neoplasms, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Predictive markers, Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors [CHEMICALS AND DRUGS], General Biochemistry, Genetics and Molecular Biology, Càncer de mama, Phosphatidylinositol 3-Kinases, Text mining, Breast cancer, Er breast cancer, Medicine, Humans, Cancer models, neoplasms, Protein Kinase Inhibitors, Resistència als medicaments, fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos::resistencia a los antineoplásicos [FENÓMENOS Y PROCESOS], neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Multidisciplinary, Manchester Cancer Research Centre, acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas [COMPUESTOS QUÍMICOS Y DROGAS], business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Inhibitor resistance, Cyclin-Dependent Kinase 4, General Chemistry, Cyclin-Dependent Kinase 6, Proteïnes quinases - Inhibidors, Retinoblastoma Binding Proteins, Receptors, Estrogen, Drug Resistance, Neoplasm, Drug resistance, Mama - Càncer - Tractament, Cancer research, Female, business, Biomarkers
Abstract

CDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast cancer. Some of these tumors are de novo resistant to CDK4/6 inhibitors and others develop acquired resistance. Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n = 37) and estrogen receptor-positive breast cancer cell lines, as well as reduced response of early and advanced breast cancer patients to CDK4/6 inhibitors (n = 89). We also identified heterozygous RB1 loss as biomarker of acquired resistance and poor clinical outcome. Combination of the CDK4/6 inhibitor ribociclib with the PI3K inhibitor alpelisib showed antitumor activity in estrogen receptor-positive non-basal-like breast cancer patient-derived xenografts, independently of PIK3CA, ESR1 or RB1 mutation, also in drug de-escalation experiments or omitting endocrine therapy. Our results offer insights into predicting primary/acquired resistance to CDK4/6 inhibitors and post-progression therapeutic strategies. This study has been supported by the Susan G. Komen Foundation (CCR15330331) and by the Catalan Agency AGAUR (2017 SGR 540) [to V.S.]. V.S. received funds from the Instituto de Salud Carlos III: grants PI13/01714, CP14/00228, MV15/00041, CPII19/00033 and PI20/00892. M.P. received a Juan de la Cierva Grant from the Ministerio de Economía y Competitividad (FJCI-2015-25412), L.Mo. a grant from FI-AGAUR (2019 FI_B 01199), F.B-M. a grant from the Fundación Científica Asociación Española Contra el Cáncer (AECC_Postdoctoral17-1062) and M.S-G, a Marie Slodowska-Curie Innovative Training Networks PhD fellowship (H2020-MSCA-ITN-2015_675392). This work was supported by Breast Cancer Research Foundation (BCRF-19-08), Instituto de Salud Carlos III Project Reference number AC15/00062 and the EC under the framework of the ERA-NET TRANSCAN-2 initiative co-financed by FEDER, Instituto de Salud Carlos III (CB16/12/00449 and PI19/01181) and Asociación Española Contra el Cáncer (to J.A.). R.B.C. laboratory is supported by Breast Cancer Now (grant numbers: MAN-Q1 and MAN-Q2), NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007) and EdiREX Horizon 2020 grant No.731105. The xenograft program in the C.C. laboratory is supported by Cancer Research UK and also received funding from an EU H2020 Network of Excellence (EuroCAN). This work has been supported by NIH grants P30 CA008748 and RO1CA190642-01, the CDMRP grant BC171535P1, and the Breast Cancer Research Foundation [to M.S.]. A.P. received funds from Instituto de Salud Carlos III—PI16/00904 and PI19/01846, Breast Cancer Now—2018NOVPCC1294, Breast Cancer Research Foundation-AACR Career Development Awards for Translational Breast Cancer Research 19-20-26-PRAT, Fundació La Marató TV3 201935-30, the European Union’s Horizon 2020 research and innovation program H2020-SC1-BHC-2018-2020. IRB Barcelona is a recipient of a Severo Ochoa Centre of Excellence Award from the Spanish Ministry of Economy and Competitiveness (MINECO; Government of Spain) and is supported by CERCA (Generalitat de Catalunya). C. S. Verma reports grants from MSD International and grants from Ipsen outside the submitted work.

Published
2022
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197. Identification of a Molecularly-Defined Subset of Breast and Ovarian Cancer Models that Respond to WEE1 or ATR Inhibition, Overcoming PARP Inhibitor Resistance

Author

Violeta Serra, Anderson T. Wang, Marta Castroviejo-Bermejo, Urszula M. Polanska, Marta Palafox, Andrea Herencia-Ropero, Gemma N. Jones, Zhongwu Lai, Joshua Armenia, Filippos Michopoulos, Alba Llop-Guevara, Rachel Brough, Aditi Gulati, Stephen J. Pettitt, Krishna C. Bulusu, Jenni Nikkilä, Zena Wilson, Adina Hughes, Paul W.G. Wijnhoven, Ambar Ahmed, Alejandra Bruna, Albert Gris-Oliver, Marta Guzman, Olga Rodríguez, Judit Grueso, Joaquin Arribas, Javier Cortés, Cristina Saura, Alan Lau, Susan Critchlow, Brian Dougherty, Carlos Caldas, Gordon B. Mills, J. Carl Barrett, Josep V. Forment, Elaine Cadogan, Christopher J. Lord, Cristina Cruz, Judith Balmaña, Mark J. O'Connor, Institut Català de la Salut, [Serra V] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. CIBERONC, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Wang AT, Polanska UM] AstraZeneca Oncology R&D, Cambridge, United Kingdom. [Castroviejo-Bermejo M, Palafox M, Llop-Guevara A, Guzman M, Rodríguez O, Grueso J] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Herencia-Ropero A] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Arribas J] CIBERONC, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Growth Factors Laboratory, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Cortés J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Saura C] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Breast Cancer and Melanoma Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Cruz C] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. High Risk and Familial Cancer, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Balmaña J] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. High Risk and Familial Cancer, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Cancer Research, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Antineoplastic Agents, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES], Carcinoma, Ovarian Epithelial, Poly(ADP-ribose) Polymerase Inhibitors, Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors [CHEMICALS AND DRUGS], Humans, Other subheadings::/therapeutic use [Other subheadings], Protein Kinase Inhibitors, Ovarian Neoplasms, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas [COMPUESTOS QUÍMICOS Y DROGAS], Otros calificadores::/uso terapéutico [Otros calificadores], BRCA1 Protein, Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES], Nucleosides, Ovaris - Càncer - Tractament, Protein-Tyrosine Kinases, Oncology, Mama - Càncer - Tractament, Phthalazines, Female, Biomarkers, Proteïnes quinases - Inhibidors - Ús terapèutic
Abstract

Cáncer de mama y de ovario; Inhibición WEE1 Càncer de mama i d'ovari; Inhibició WEE1 Breast and ovarian cancer; WEE1 inhibition Purpose: PARP inhibitors (PARPi) induce synthetic lethality in homologous recombination repair (HRR)-deficient tumors and are used to treat breast, ovarian, pancreatic, and prostate cancers. Multiple PARPi resistance mechanisms exist, most resulting in restoration of HRR and protection of stalled replication forks. ATR inhibition was highlighted as a unique approach to reverse both aspects of resistance. Recently, however, a PARPi/WEE1 inhibitor (WEE1i) combination demonstrated enhanced antitumor activity associated with the induction of replication stress, suggesting another approach to tackling PARPi resistance. Experimental Design: We analyzed breast and ovarian patient-derived xenoimplant models resistant to PARPi to quantify WEE1i and ATR inhibitor (ATRi) responses as single agents and in combination with PARPi. Biomarker analysis was conducted at the genetic and protein level. Metabolite analysis by mass spectrometry and nucleoside rescue experiments ex vivo were also conducted in patient-derived models. Results: Although WEE1i response was linked to markers of replication stress, including STK11/RB1 and phospho-RPA, ATRi response associated with ATM mutation. When combined with olaparib, WEE1i could be differentiated from the ATRi/olaparib combination, providing distinct therapeutic strategies to overcome PARPi resistance by targeting the replication stress response. Mechanistically, WEE1i sensitivity was associated with shortage of the dNTP pool and a concomitant increase in replication stress. Conclusions: Targeting the replication stress response is a valid therapeutic option to overcome PARPi resistance including tumors without an underlying HRR deficiency. These preclinical insights are now being tested in several clinical trials where the PARPi is administered with either the WEE1i or the ATRi. This work was supported by the Spanish Instituto de Salud Carlos III (ISCIII), an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds (FIS PI17/01080 to V. Serra, PI12/02606 to J. Balmaña); European Research Area-NET, Transcan-2 (AC15/00063), Asociación Española contra el Cáncer (AECC; LABAE16020PORTT), the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR; 2017 SGR 540), La Marató TV3 (654/C/2019), and ERAPERMED2019–215 to V. Serra. We also acknowledge the GHD-Pink program, the FERO Foundation, and the Orozco Family for supporting this study (to V. Serra). V. Serra was supported by the Miguel Servet Program (ISCIII; CPII19/00033); M. Castroviejo-Bermejo and C. Cruz (AIOC15152806CRUZ) by AECC; A. Herencia-Ropero by Generalitat de Catalunya-PERIS (SLT017/20/000081); M. Palafox by Juan de la Cierva (FJCI-2015–25412); A. Lau by AECC and Generalitat de Catalunya-PERIS (INVES20095LLOP, SLT002/16/00477); A. Gris-Oliver by FI-AGAUR (2015 FI_B 01075). This work was supported by Breast Cancer Research Foundation (BCRF-19–08), Instituto de Salud Carlos III Project Reference number AC15/00062, and the EC under the framework of the ERA-NET TRANSCAN-2 initiative co-financed by FEDER, Instituto de Salud Carlos III (CB16/12/00449 and PI19/01181), and Asociación Española Contra el Cáncer (to J. Arribas). The xenograft program in the Caldas laboratory was supported by Cancer Research UK and also received funding from an EU H2020 Network of Excellence (EuroCAN). The RPPA facility is funded by NCI #CA16672.

Published
2022

198. Synthesis of new non-covered and silica-covered Y0.9Tm0.1-xYbxVO4 nanophosphors with emission in the visible and NIR ranges.

Author

Lozano, Y., Isasi, J., Fernández-Ramos, M., Rapp, M., Palafox, M. Alcolea, Ortiz-Rivero, E., and Muñoz-Ortiz, T.

Subjects
*HYDROTHERMAL synthesis, *X-ray diffraction, *FOURIER transform infrared spectroscopy, *TRANSMISSION electron microscopy, *SOL-gel processes
Abstract

The development of new materials of interest in the bioimaging field is a relevant topic in current research. We present and study here novel non-covered and silica-covered Y 0. 9 Tm 0.1-x Yb x VO 4 samples with x = 0, 0.01, 0.05 and 0.09 that were prepared by hydrothermal synthesis. For comparison purposes, the study of Y 0. 9 Tm 0. 1 VO 4 sample synthesized by the sol-gel method was also included. The relationships between the synthesis method, dopant content and luminescence emission were systematically studied by X-ray diffraction (XRD), FTIR spectroscopy and transmission electron microscopy (TEM). XRD profiles and FTIR spectra confirm the zircon-type structure of the obtained samples. Particles of two different morphologies were found in TEM images of uncoated samples, some spherical with sizes between 42 and 50 nm and others elongated. A shell thickness between 8 and 13 nm was also observed in silica-covered samples. Photoluminescence studies of our samples revealed emission in the NIR and visible ranges. Under excitation at 790 nm, the spectra of thulium-doped samples showed the characteristic emission band of Tm3+ ions. Substitution of thulium by ytterbium successfully led to an up-conversion emission under excitation at 980 nm. Finally, the fluorescent emission study in the NIR of samples that could be more biocompatible demonstrated that they are suitable for use as luminescent thermometers in the physiological temperature range. • Y 0·9 Tm 0.1−x Yb x VO 4 samples with x = 0, 0.01, 0.05 and 0.09 were successfully obtained as pure phases by hydrothermal and sol-gel synthesis methods. • XRD profiles and FTIR spectra confirmed the zircon-type structure of the synthetized samples. • A shell of 8–13 nm thickness was found in silica-covered samples. • Obtained samples showed emission in the NIR and visible ranges. Substitution of Tm3+ by Yb3+ led to up-conversion emission. • Silica-covered co-doped samples are suitable for use as luminescent thermometers within the physiological temperature range. [ABSTRACT FROM AUTHOR]

Published
2023
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199. INK4 Tumor Suppressor Proteins Mediate Resistance to CDK4/6 Kinase Inhibitors

Author

Matthew G. Rees, Nathanael S. Gray, Zhiqiang Li, Katherine A. Donovan, Pedram Razavi, Hong Shao, Eric S. Fischer, Neal Rosen, Jennifer Roth, Qing Chang, Melissa M. Ronan, Jiaye Guo, Qing X. Li, Andrew S Boghossian, Sarat Chandarlapaty, Violeta Serra, John D. Chodera, Baishan Jiang, Isabella S Del Priore, Andrew Koff, Elisa de Stanchina, Bo Liu, Jorge S. Reis-Filho, Rei Kudo, Marta Palafox, Institut Català de la Salut, [Li Q, Shao H, Del Priore IS] Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York. [Jiang B] Department of Cancer Biology, DanaFarber Cancer Institute, Boston, Massachusetts. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts. [Guo J] Computational & Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York. [Chang Q] Anti-Tumor Assessment, Memorial Sloan Kettering Cancer Center, New York, New York. [Palafox M, Serra V] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Pyridines, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Antineoplastic Agents, Breast Neoplasms, Drug resistance, Palbociclib, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors [CHEMICALS AND DRUGS], Piperazines, Article, Downregulation and upregulation, In vivo, Cell Line, Tumor, PTEN, Humans, Other subheadings::/therapeutic use [Other subheadings], Protein Kinase Inhibitors, Cyclin-Dependent Kinase Inhibitor Proteins, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], integumentary system, biology, Chemistry, Kinase, acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas [COMPUESTOS QUÍMICOS Y DROGAS], Otros calificadores::/uso terapéutico [Otros calificadores], Tumor Suppressor Proteins, Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Tumor Suppressor Proteins [CHEMICALS AND DRUGS], Oncology, Proteïnes tumorals, Drug Resistance, Neoplasm, Mama - Càncer - Tractament, biology.protein, Cancer research, Female, Cyclin-dependent kinase 6, biological phenomena, cell phenomena, and immunity, aminoácidos, péptidos y proteínas::proteínas::proteínas de neoplasias::proteínas supresoras de tumor [COMPUESTOS QUÍMICOS Y DROGAS], CDK inhibitor, Proteïnes quinases - Inhibidors - Ús terapèutic
Abstract

Proteïnes supressores de tumors; Inhibidors de la quinasa Proteínas supresoras de tumores; Inhibidores de la quinasa Tumor suppressor proteins; Kinase inhibitors Cyclin-dependent kinases 4 and 6 (CDK4/6) represent a major therapeutic vulnerability for breast cancer. The kinases are clinically targeted via ATP competitive inhibitors (CDK4/6i); however, drug resistance commonly emerges over time. To understand CDK4/6i resistance, we surveyed over 1,300 breast cancers and identified several genetic alterations (e.g., FAT1, PTEN, or ARID1A loss) converging on upregulation of CDK6. Mechanistically, we demonstrate CDK6 causes resistance by inducing and binding CDK inhibitor INK4 proteins (e.g., p18INK4C). In vitro binding and kinase assays together with physical modeling reveal that the p18INK4C–cyclin D–CDK6 complex occludes CDK4/6i binding while only weakly suppressing ATP binding. Suppression of INK4 expression or its binding to CDK6 restores CDK4/6i sensitivity. To overcome this constraint, we developed bifunctional degraders conjugating palbociclib with E3 ligands. Two resulting lead compounds potently degraded CDK4/6, leading to substantial antitumor effects in vivo, demonstrating the promising therapeutic potential for retargeting CDK4/6 despite CDK4/6i resistance. Significance: CDK4/6 kinase activation represents a common mechanism by which oncogenic signaling induces proliferation and is potentially targetable by ATP competitive inhibitors. We identify a CDK6–INK4 complex that is resilient to current-generation inhibitors and develop a new strategy for more effective inhibition of CDK4/6 kinases. The Chandarlapaty lab has received generous funding support for this research from the Cancer Couch Foundation, the Shen Family Fund, the Smith Fund for Cancer Research, the Breast Cancer Research Foundation, an NIH Cancer Center Support Grant (P30 CA008748), and NIH R01234361. Q. Li has received support from Translational Research Oncology Training Fellowship (MSKCC) made possible by the generous contribution of First Eagle Investment Management. V. Serra reports grants from the Susan G. Komen Foundation (CCR15330331) and Instituto de Salud Carlos III (CPII19/00033) during the conduct of the study and grants from Novartis, Genentech, and AstraZeneca outside the submitted work. The Chodera laboratory receives or has received funding from multiple sources, including the NIH and an NIH Cancer Center Support Grant (P30 CA008748), the National Science Foundation, the Parker Institute for Cancer Immunotherapy, Relay Therapeutics, Entasis Therapeutics, Silicon Therapeutics, EMD Serono (Merck KGaA), AstraZeneca, Vir Biotechnology, Bayer, XtalPi, Foresite Laboratories, the Molecular Sciences Software Institute, the Starr Cancer Consortium, the Open Force Field Consortium, Cycle for Survival, a Louis V. Gerstner Young Investigator Award, and the Sloan Kettering Institute. J. Guo acknowledges support from NIH grant R01 GM121505. J.D. Chodera acknowledges support from NIH grant P30 CA008748, NIH grant R01 GM121505, and NIH grant R01 GM132386. A complete funding history for the Chodera lab can be found at http://choderalab.org/funding, including complete funding information and grant numbers. The authors thank Dr. Marie Will and Madeline Dorso for helpful comments on the manuscript and Dr. Zhan Yao for helpful advice on the kinase assays.

Published
2020

200. Personalized cancer therapy prioritization based on driver alteration co-occurrence patterns

Author

Pedram Razavi, Patrick Aloy, Maurizio Scaltriti, Lidia Mateo, Miquel Duran-Frigola, Joaquín Arribas, Meritxell Bellet, Sarat Chandarlapaty, Marta Palafox, Albert Gris-Oliver, Violeta Serra, Institut Català de la Salut, [Mateo L, Duran-Frigola M] Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain. [Gris-Oliver A, Palafox M] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Scaltriti M] Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. Department of Pathology, MSKC C, New York, NY 10065, USA. [Razavi P] Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. Breast Medicine Service, Department of Medicine, MSKCC and Weill-Cornell Medical College, New York, NY 10065, USA. [Arribas J] Growth Factors Laboratory, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain. CIBERONC, Barcelona, Spain. [Bellet M] Breast Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Serra V] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. CIBERONC, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Genomic profiling, Databases, Factual, Oncologia, Computer science, Method, lcsh:Medicine, Genome, Translational Research, Biomedical, Drug-response biomarkers, 0302 clinical medicine, Survival data, terapéutica::medicina de precisión [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Neoplasms, Profiling (information science), Medicina personalitzada, Precision Medicine, Genetics (clinical), Otros calificadores::/terapia [Otros calificadores], 0303 health sciences, Càncer - Tractament, Disease Management, Precision oncology, Genomics, 3. Good health, Gene Expression Regulation, Neoplastic, Identification (information), Treatment Outcome, 030220 oncology & carcinogenesis, Biomarker (medicine), Molecular Medicine, Càncer -- Tractament, Therapeutics::Precision Medicine [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Algorithms, Prioritization, lcsh:QH426-470, Systems biology, Clinical Decision-Making, Cancer therapy, Antineoplastic Agents, Computational biology, neoplasias [ENFERMEDADES], 03 medical and health sciences, In vivo, Biomarkers, Tumor, medicine, Genetics, Humans, Tumor growth, Progression-free survival, Molecular Biology, 030304 developmental biology, lcsh:R, Co-occurrence, Reproducibility of Results, Cancer, Oncogenes, Other subheadings::/therapy [Other subheadings], Models, Theoretical, medicine.disease, Human genetics, Clinical trial, Neoplasms [DISEASES], lcsh:Genetics, Genòmica, Drug Resistance, Neoplasm, Driver co-occurrence networks
Abstract

Molecular profiling of personal cancer genomes, and the identification of actionable vulnerabilities and drug-response biomarkers, are the basis of precision oncology. Tumors often present several driver alterations that might be connected by cross-talk and feedback mechanisms, making it difficult to mark single oncogenic variations as reliable predictors of therapeutic outcome. In the current work, we uncover and exploit driver alteration co-occurrence patterns from a recently published in vivo screening in patient-derived xenografts (PDXs), including 187 tumors and 53 drugs. For each treatment, we compare the mutational profiles of sensitive and resistant PDXs to statistically define Driver Co-Occurrence (DCO) networks, which capture both genomic structure and putative oncogenic synergy. We then use the DCO networks to train classifiers that can prioritize, among the available options, the best possible treatment for each tumor based on its oncogenomic profile. In a cross-validation setting, our drug-response models are able to correctly predict 66% of sensitive and 77% of resistant drug-tumor pairs, based on tumor growth variation. Perhaps more interesting, our models are applicable to several tumor types and drug classes for which no biomarker has yet been described. Additionally, we experimentally validated the performance of our models on 15 new tumor samples engrafted in mice, achieving an overall accuracy of 75%. Finally, we adapted our strategy to derive drug-response models from continuous clinical outcome measures, such as progression free survival, which better represent the data acquired during routine clinical practice and in clinical trials. We believe that the computational framework presented here could be incorporated into the design of adaptive clinical trials, revealing unexpected connections between oncogenic alterations and increasing the clinical impact of genomic profiling.

Published
2020

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