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1.
Exp Cell Res ; 430(1): 113722, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37442265

RESUMEN

Osimertinib is a third-generation epidermal growth factor receptor (EGFR)1 tyrosine kinase inhibitor (TKI) approved for the treatment of EGFR-positive patients exhibiting a T790 M resistance mutation after treatment with an earlier generation of EGFR TKIs. However, resistance to osimertinib inevitably develops despite its efficacy, and the resistance mechanisms are complex and not fully understood. We established cell lines with acquired resistance to osimertinib from gefitinib- or erlotinib-resistant NSCLC cells using a dose-escalation method, and found that they had upregulated levels of phosphorylated ERK1/2. Targeted next-generation sequencing of 143 genes was performed, and interestingly, amplification of KRAS was observed in osimertinib-resistant cells. Transfection of siRNA against the KRAS gene notably reduced the activation of ERK1/2 and AKT and significantly enhanced the induction of apoptosis by osimertinib treatment in osimertinib-resistant cells. LY3009120, a RAF inhibitor, showed a significant synergistic effect with osimertinib on apoptotic cell death in osimertinib-resistant cells. Combined treatment with osimertinib and LY3009120 also demonstrated remarkable synergistic anti-tumor activity in mouse xenografts of these cells. This could be a potential new treatment option for KRAS amplification-induced osimertinib failure.


Asunto(s)
Neoplasias Pulmonares , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Animales , Ratones , Proteínas Proto-Oncogénicas p21(ras)/genética , Resistencia a Antineoplásicos/genética , Línea Celular Tumoral , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Compuestos de Anilina/farmacología , Receptores ErbB/genética , Inhibidores de Proteínas Quinasas/farmacología , Mutación
2.
J Cancer Educ ; 39(3): 335-348, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38594385

RESUMEN

Cancer survivors including Asian American breast cancer survivors have reported their high needs for help during their survivorship process. With the COVID-19 pandemic, the necessity of technology-based programs to address their needs for help without face-to-face interactions has been highlighted. The purpose of this randomized intervention study was to determine the efficacy of a technology-based program in reducing various types of needs for help among this specific population. This was a randomized clinical trial with repeated measures. A total of 199 participants were included in the data analysis. The recruitment settings included both online and offline communities/groups for Asian Americans. The needs for help were assessed using the Support Care Needs Survey-34 Short Form (SCNS) subscales measuring psychological, information, physical, support, and communication needs. Data analysis was conducted through an intent-to-treat approach. In the mixed effect models, psychological needs, information needs, physical needs, and communication needs decreased over time (P < .001). However, there were no significant group * time effects. Social support significantly mediated the effects of a technology-based intervention on psychological, information, and support needs at the pre-test and the post-1 month. This study supported significant decreases in the needs for help of Asian American breast cancer survivors by a technology-based intervention. Further studies are needed with other racial/ethnic groups of cancer survivors to confirm the efficacy of a technology-based intervention in reducing cancer survivors' needs for help during their survivorship process.


Asunto(s)
Asiático , Neoplasias de la Mama , COVID-19 , Supervivientes de Cáncer , Apoyo Social , Humanos , Femenino , Neoplasias de la Mama/etnología , Neoplasias de la Mama/psicología , Neoplasias de la Mama/terapia , Supervivientes de Cáncer/psicología , Asiático/psicología , Persona de Mediana Edad , COVID-19/prevención & control , COVID-19/epidemiología , Evaluación de Necesidades , Adulto , SARS-CoV-2 , Necesidades y Demandas de Servicios de Salud , Anciano , Encuestas y Cuestionarios
3.
Comput Inform Nurs ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38913997

RESUMEN

The number of health technology-based intervention studies has grown significantly. However, issues in the recruitment and retention for such studies, especially of Asian Americans, have rarely been discussed. The purpose of this paper was to discuss issues in the recruitment and retention of a specific group of Asian Americans-Korean American midlife women with depressive symptoms-into a technology-based intervention study using computers and mobile devices with a measurement device and to provide directions for future participant recruitment and retention in technology-based intervention studies. The written memos of research team members and the written records of research team meetings were analyzed using a content analysis. The issues in the recruitment and retention process included (1) low recruitment and retention rates; (2) the perceived long intervention period; (3) strict inclusion/exclusion criteria; (4) concerns related to the use of a measurement device; and (5) the perceived adequacy of monetary incentives. Based on the issues identified in the study, several suggestions are made for future recruitment and retention of racial/ethnic minorities in technology-based intervention studies (eg, appropriate intervention period, innovative and creative motivation strategies, acceptable measurement scales and devices, and adequate monetary reimbursement).

4.
BMC Womens Health ; 22(1): 51, 2022 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-35197031

RESUMEN

BACKGROUND: Human papillomavirus (HPV) vaccination is a form of primary prevention for cervical cancer. The HPV vaccination rate of female university students is not high in Korea and China. Therefore, the purpose of this study was to identify and compare the factors associated with intention to receive HPV vaccination between Korean and Chinese female university students. METHODS: The participants were 273 Korean and 317 Chinese female university students who had not been vaccinated for HPV, and data were collected using a self-reported questionnaire about attitudes toward HPV vaccination, HPV knowledge, perceptions of HPV infection, and intention to receive HPV vaccine. RESULTS: There were no significant differences between the Korean and Chinese female university students in HPV knowledge, attitudes, perceptions, and vaccination intention. The factors influencing the intention of HPV vaccination in Korean students were a positive attitude toward the HPV vaccine and a high HPV knowledge score. For Chinese students, sexual experience, awareness of genital warts, a positive attitude toward the HPV vaccine, a high HPV knowledge scores, a perception of the seriousness of HPV infection, and negative emotions regarding HPV infection were significant factors. CONCLUSIONS: It is important to improve attitudes and knowledge about HPV and the HPV vaccine in order to enhance HPV vaccination both in Korea and China. Perceived seriousness and negative emotions regarding HPV infection should be used as a framework to develop subject-tailored interventions in China.


Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , China , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/uso terapéutico , Aceptación de la Atención de Salud , República de Corea , Estudiantes , Encuestas y Cuestionarios , Universidades , Neoplasias del Cuello Uterino/prevención & control , Vacunación
5.
Geriatr Nurs ; 48: 296-302, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36335856

RESUMEN

This study aimed to explore racial/ethnic differences in the attitudes toward Alzheimer's Disease (AD) and dementia caregiving among midlife women who were family caregivers of persons living with AD (MWPLAD) in the U.S. and examine the associations of the attitudes to their health outcomes. This was a cross-sectional online survey study among 172 MWPLAD. The instruments included: the Attitude toward AD and Related Dementias Scale, the Questions on Attitudes toward AD Caregiving, the Social Readjustment Rating Scale, the EQ-5D-5L and the Midlife Women's Symptom Index. Multiple linear regression analyses were conducted. There were significant racial/ethnic differences in caregivers' attitudes toward dementia caregiving, health-related quality of life, and total severity scores of symptoms (p < .01). Controlling for covariates including race/ethnicity, caregivers' positive attitudes toward dementia caregiving were significantly associated with their health outcomes (p ≤ .05). Interventions for MWPLAD need to consider racial/ethnical differences in their attitudes toward dementia caregiving.


Asunto(s)
Enfermedad de Alzheimer , Femenino , Humanos , Calidad de Vida , Estudios Transversales , Cuidadores , Encuestas y Cuestionarios
6.
Org Biomol Chem ; 19(35): 7655-7663, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34524343

RESUMEN

A novel synthetic strategy for highly enantioenriched cis-3,5-disubstituted γ-lactones has been developed by the AgOTf-promoted nucleophilic substitution of α-bromoacetates with silyl enol ethers and subsequent reductive lactonization. The utility of this synthetic method was further demonstrated through the concise stereodivergent synthesis of cis- and trans-2,4-disubstituted tetrahydrofurans.

7.
Proc Natl Acad Sci U S A ; 114(43): 11422-11427, 2017 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-29073066

RESUMEN

Tumor necrosis factor (TNF)-receptor associated factor 4 (TRAF4), an adaptor protein with E3-ligase activity, is involved in embryogenesis, cancer initiation and progression, and platelet receptor (GPIb-IX-V complex and GPVI)-mediated signaling for reactive oxygen species (ROS) production that initiates thrombosis at arterial shears. Disruption of platelet receptors and the TRAF4 interaction is a potential target for therapeutic intervention by antithrombotic drugs. Here, we report a crystal structure of TRAF4 (amino acid residues 290∼470) in complex with a peptide from the GPIbß receptor (amino acid residues 177∼181). The GPIbß peptide binds to a unique shallow surface composed of two hydrophobic pockets on TRAF4. Further studies revealed the TRAF4-binding motif Arg-Leu-X-Ala. The TRAF4-binding motif was present not only in platelet receptors but also in the TGF-ß receptor. The current structure will provide a template for furthering our understanding of the receptor-binding specificity of TRAF4, TRAF4-mediated signaling, and related diseases.


Asunto(s)
Complejo GPIb-IX de Glicoproteína Plaquetaria/química , Glicoproteínas de Membrana Plaquetaria/química , Factor 4 Asociado a Receptor de TNF/química , Calorimetría/métodos , Modelos Moleculares , Complejo GPIb-IX de Glicoproteína Plaquetaria/metabolismo , Glicoproteínas de Membrana Plaquetaria/metabolismo , Conformación Proteica , Transducción de Señal , Factor 4 Asociado a Receptor de TNF/metabolismo
8.
Carcinogenesis ; 36 Suppl 1: S89-110, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26106145

RESUMEN

Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental carcinogenesis.


Asunto(s)
Carcinogénesis/inducido químicamente , Carcinógenos Ambientales/efectos adversos , Muerte Celular/efectos de los fármacos , Exposición a Riesgos Ambientales/efectos adversos , Sustancias Peligrosas/efectos adversos , Neoplasias/inducido químicamente , Neoplasias/etiología , Animales , Homeostasis/efectos de los fármacos , Humanos
9.
Int J Cancer ; 136(11): 2717-29, 2015 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-25382705

RESUMEN

To overcome T790M-mediated acquired resistance of lung cancer cells to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), second generation TKIs such as BIBW2992 (afatinib) and third generation TKIs including WZ4002 have been developed. However, clinical data on their efficacy in treating T790M mutant tumors are lacking. Histone deacetylase (HDAC) inhibitors have been reported to arrest cell growth and to lead to differentiation and apoptosis of various cancer cells, both in vitro and in vivo. In the present study, we assessed whether the combination of suberoylanilide hydroxamic acid (SAHA, vorinostat), a potent HDAC inhibitor, and BIBW2992 or WZ4002 could overcome EGFR TKI resistance associated with T790M mutation in lung cancer cells. While treatment with BIBW2992 or WZ4002 alone slightly reduced the viability of PC-9G and H1975 cells, which possess T790M mutation, combining them with SAHA resulted in significantly decreased cell viability through the activation of the apoptotic pathway. This combination also enhanced autophagy occurrence and inhibition of autophagy significantly reduced the apoptosis induced by the combination treatment, showing that autophagy is required for the enhanced apoptosis. Caspase-independent autophagic cell death was also induced by the combination treatment with SAHA and either BIBW2992 or WZ4002. Finally, the combined treatment with SAHA and either BIBW2992 or WZ4002 showed an enhanced anti-tumor effect on xenografts of H1975 cells in vivo. In conclusion, the combination of new generation EGFR TKIs and SAHA may be a new strategy to overcome the acquired resistance to EGFR TKIs in T790M mutant lung cancer.


Asunto(s)
Resistencia a Antineoplásicos/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Receptores ErbB/genética , Ácidos Hidroxámicos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Acrilamidas/farmacología , Afatinib , Animales , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptosis , Autofagia , Caspasas/metabolismo , Línea Celular Tumoral , Sinergismo Farmacológico , Receptores ErbB/antagonistas & inhibidores , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/genética , Ratones , Mutación , Trasplante de Neoplasias , Pirimidinas/farmacología , Quinazolinas/farmacología , Vorinostat , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Biotechnol Bioeng ; 112(2): 416-21, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25163446

RESUMEN

L-ornithine is a non-essential amino acid for various industrial applications in food industry. In this study, Corynebacterium glutamicum ATCC 13032 was metabolically engineered for the production of L-ornithine. First, the proB and argF genes were deleted to block the competitive branch pathway and to block the conversion of L-ornithine to citrulline, respectively. In addition, the argR gene encoding the regulatory repressor of the L-arginine operon was also deleted. The resulting strain produced 230 mg/L of L-ornithine from glucose in flask culture. This base strain was further engineered by the plasmid-based overexpression of the argCJBD genes from C. glutamicum ATCC 21831, which resulted in the production of 7.19 g/L of L-ornithine. To enrich the NADPH pool, the carbon flux was redirected towards the pentose phosphate pathway by changing the start codons of the pgi and zwf genes and replacing the native promoter of the tkt operon with the strong sod promoter. Fed-batch cultivation of this final strain YW06 (pSY223) allowed production of 51.5 g/L of L-ornithine in 40 h with the overall productivity of 1.29 g/L/h. The results obtained in this study demonstrate the possibility of efficiently producing L-ornithine by metabolically engineered C. glutamicum.


Asunto(s)
Corynebacterium glutamicum/metabolismo , Ingeniería Metabólica/métodos , Ornitina/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Corynebacterium glutamicum/genética , Fermentación , Redes y Vías Metabólicas
11.
Cancer Nurs ; 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38656247

RESUMEN

BACKGROUND: Despite increased research on breast cancer survivors, little is known about how socio-behavioral factors influence the symptoms among racial/ethnic minority breast cancer survivors, particularly Asian American breast cancer survivors (AABCS). OBJECTIVE: This study examined the relationship between multiple socio-behavioral factors in AABCS, including attitudes, perceived barriers, and social influences, and their symptom experiences, with an emphasis on the mediating effect of self-efficacy. METHODS: This secondary analysis used data collected from 195 AABCS women recruited through online and offline communities from January 2017 to June 2020. Study variables were measured using validated instruments such as the Questions on Attitudes, Self-Efficacy, Perceived Barriers, and Social Influences; the Cancer Behavior Inventory; and the Memorial Symptom Assessment Scale-Short Form. For structural equation modeling based on Bandura's self-efficacy theory, mediation analysis was performed using SPSS version 26.0 and AMOS 28. RESULTS: The overall fitness of the hypothetical model to the data is acceptable (χ2 = 51.36, P < .001; goodness-of-fit index = 0.95, adjusted goodness-of-fit index = 0.89, comparative fit index = 0.96, Tucker-Lewis index = 0.94, normed fit index = 0.94, and root-mean-square error of approximation index = 0.08). Both attitudes and social influences indirectly influenced symptom distress through self-efficacy (ß = -0.054, P = .019, and ß = -0.053, P = .017, respectively). Perceived barriers had indirect effects through self-efficacy (ß = 0.121, P = .024) and significant direct effects (ß = 0.605, P = .003) on symptom distress. CONCLUSIONS: Our findings supported that the self-efficacy for coping mediated their symptom experience among AABCS. In addition, there were significant relationships among attitudes, perceived barriers, social influences, and symptom experience. IMPLICATIONS FOR PRACTICE: Future theory-driven interventions need to consider self-efficacy and socio-behavioral factors in symptom management among AABCS.

12.
J Korean Med Sci ; 28(3): 378-82, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23486643

RESUMEN

Although gemifloxacin has low in vitro activity against Mycobacterium tuberculosis, the effect of gemifloxacin on the delay of tuberculosis (TB) treatment has not been validated in a clinical setting. The study group included patients with culture-confirmed pulmonary TB who initially received gemifloxacin for suspected community-acquired pneumonia (CAP). Two control groups contained patients treated with other fluoroquinolones or nonfluoroquinolone antibiotics. Sixteen cases were treated with gemifloxacin for suspected CAP before TB diagnosis. Sixteen and 32 patients were treated with other fluoroquinolones and nonfluoroquinolones, respectively. The median period from the initiation of antibiotics to the administration of anti-TB medication was nine days in the gemifloxacin group, which was significantly different from the other fluoroquinolones group (35 days). The median times for the nonfluoroquinolone group and the gemifloxacin group were not significantly different. There were no significant differences between the gemifloxacin and other fluoroquinolone group in terms of symptomatic and radiographic improvements. However, the frequency of radiographic improvement in the other fluoroquinolones group tended to be higher than in the gemifloxacin group. Gemifloxacin might be the preferred fluoroquinolone for treating CAP, to alleviate any concerns about delaying TB treatment.


Asunto(s)
Antibacterianos/uso terapéutico , Fluoroquinolonas/uso terapéutico , Naftiridinas/uso terapéutico , Tuberculosis/tratamiento farmacológico , Adulto , Anciano , Estudios de Casos y Controles , Gemifloxacina , Humanos , Persona de Mediana Edad , Neumonía/complicaciones , Neumonía/diagnóstico , Radiografía , Tuberculosis/complicaciones , Tuberculosis/diagnóstico por imagen
13.
Arch Public Health ; 81(1): 110, 2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37328899

RESUMEN

BACKGROUND: South Korea is a country with a very low fertility rate and there is a tendency for young adults to postpone marriage and childbirth, which affects adverse pregnancy outcomes. It is important for young adults to predict and prepare in advance for future fertility-related issues, especially by identifying their willingness and thoughts about childbirth for both women and men. This study aimed to investigate gender differences in willingness for childbirth, fertility knowledge, and the value of motherhood or fatherhood among college students in South Korea and to explore the factors influencing willingness for childbirth. METHODS: This was a cross sectional study among 286 unmarried college students who were recruited through a campus email and online communities for college student conducted from June 20, 2021 to July 19, 2021. The data were analyzed using the chi-square test and t-test to identify gender differences in general characteristics, willingness for childbirth, fertility knowledge, and value of motherhood of fatherhood. The factors influencing willingness for childbirth were examined using multiple logistic regression. RESULTS: Female students showed lower willingness for future childbirth than male students (χ2 = 26.85, p < .001). Women valued motherhood significantly less than men valued fatherhood (t = 6.34, p < .001). Women had a lower fertility knowledge score than men (t = 2.53 p = .012). The value of motherhood or fatherhood was an important influencing factor in both male and female college students (AOR = 8.57, 95% CI = 3.79-19.41 and AOR = 10.42, 95% CI = 3.65-29.80, respectively), whereas the monthly allowance was also an important influencing factor in female students (AOR = 1.02, 95% CI = 1.01-1.03). CONCLUSION: The findings indicate the future direction to develop effective interventions considering gender differences which will promote healthy pregnancy and childbirth in the future for informed reproductive decision-making for college students.

14.
Cancer Nurs ; 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37232532

RESUMEN

BACKGROUND: Despite an increasing number of culturally tailored technology-based interventions for racial/ethnic minorities, little is known about practical issues in conducting a culturally tailored technology-based intervention study among racial/ethnic minority groups, especially among Asian American colorectal cancer survivors. OBJECTIVE: The aim of this study was to describe the practical issues in conducting a study using a culturally tailored technology-based intervention among Asian American colorectal cancer survivors. METHODS: In a technology-based colorectal cancer intervention study, research team members wrote memos on issues in conducting a culturally tailored technology-based intervention study among the specific population and plausible reasons for the issues. Then, a content analysis was used to analyze the research diaries and written records of the research team. RESULTS: The practical issues found in the research process included (a) unauthentic cases, (b) a low response rate, (c) high dropout rates, (d) technological literacy, (e) language issues, (f) cultural tailoring issues, and (g) time and geographical limitations. CONCLUSIONS: These practical issues need to be considered in planning and implementing culturally tailored technology-based interventions among Asian American colorectal cancer survivors. IMPLICATIONS FOR PRACTICE: Multiple implications such as detailed information sheets, flexibility in languages, open attitudes toward cultural differences and variances, and continuous training of interventionists are proposed for culturally tailored technology-based interventions among this specific population.

15.
Nat Commun ; 14(1): 6475, 2023 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-37838727

RESUMEN

A culturally tailored virtual program could meet the survivorship needs of Asian American women breast cancer survivors (AABC). This study aims to determine the efficacy of a culturally tailored virtual information and coaching/support program (TICAA) in improving AABC's survivorship experience. A randomized clinical trial (NCT02803593) was conducted from January 2017 to June 2020 among 199 AABC. The intervention group utilized TICAA and the American Cancer Society [ACS] website while the control group used only ACS website for 12 weeks. The outcomes were measured using the SCNS-34SF (needs; primary), the MSAS-SF (symptoms; secondary), and the FACT-B (quality of life; secondary). The data were analyzed using an intent-to-treat approach. The intervention group showed significant reductions in their needs from the baseline (T0) to post 4 weeks (T1) and to post 12 weeks (T2). Although the changes were not statistically significant, the intervention group had decreased symptoms from T0 to T2 while the control group had an increase in their symptoms. The intervention group had a significant increase in their quality of life from T0 to T2. A culturally tailored virtual program could therefore improve quality of life in AABC patients. Trial Registration: To Enhance Breast Cancer Survivorship of Asian Americans (TICAA), NCT02803593, https://clinicaltrials.gov/ct2/show/NCT02803593?titles=TICAA&draw=2&rank=1.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Calidad de Vida , Femenino , Humanos , Asiático , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/etnología , Neoplasias de la Mama/terapia , Sobrevivientes , Telemedicina , Asistencia Sanitaria Culturalmente Competente , Tutoría , Apoyo Social
16.
Biochem Biophys Res Commun ; 424(2): 269-73, 2012 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-22750005

RESUMEN

The Ras small G protein-superfamily is a family of GTP hydrolases whose activity is regulated by GTP/GDP binding states. Rab6A, a member of the Ras superfamily, is involved in the regulation of vesicle trafficking, which is critical for endocytosis, biosynthesis, secretion, cell differentiation and cell growth. Rab6A exists in two isoforms, termed RabA and Rab6A'. Substitution of Gln72 to Leu72 (Q72L) at Rab6 family blocks GTP hydrolysis activity and this mutation usually causes the Rab6 protein to be constitutively in an active form. Here, we report the crystal structure of the human Rab6A'(Q72L) mutant form at 1.9Å resolution. Unexpectedly, we found that Rab6A'(Q72L) possesses GDP/Mg(2+) in the GTP binding pockets, which is formed by a flexible switch I and switch II. Large conformational changes were also detected in the switch I and switch II regions. Our structure revealed that the non-hydrolysable, constitutively active form of Rab6A' can accommodate GDP/Mg(2+) in the open conformation.


Asunto(s)
Guanosina Difosfato/química , Magnesio/química , Proteínas de Unión al GTP rab/química , Sustitución de Aminoácidos , Cristalografía por Rayos X , Glicina/química , Glicina/genética , Humanos , Leucina/química , Leucina/genética , Proteínas de Unión al GTP rab/genética
17.
J Korean Med Sci ; 26(2): 264-7, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21286019

RESUMEN

Glucocorticoids are effective for treating several respiratory diseases. However, they can cause hyperglycemia. This study determined the incidence and risk factors of steroid-induced diabetes mellitus (S-DM) in patients treated with glucocorticoid for respiratory diseases. A retrospective study examined patients with respiratory diseases treated with a prednisolone-equivalent glucocorticoid dose exceeding 20 mg/day for at least 4 weeks between January 2003 and December 2008. Patients whose initial random glucose level exceeded 200 mg/dL or who had pre-existing diabetes were excluded. S-DM was defined as a fasting glucose concentration exceeding 126 mg/dL or a random glucose concentration exceeding 200 mg/dL at least twice after beginning steroid treatment. A total of 231 patients with respiratory diseases met the inclusion criteria. Their median age was 55 yr, and 139 were female. The median cumulative prednisolone-equivalent glucocorticoid dose was 4,965 mg, and the median duration of steroid treatment was 193 days. S-DM was diagnosed in 34 (14.7%) of 231 patients. Multivariate logistic regression identified older age (odds ratio 1.05, 95% confidence interval 1.02-1.09) as a risk factor for S-DM. S-DM is frequent among patients with respiratory diseases treated with glucocorticoid. Clinicians should be aware of the possibility of S-DM, especially among elderly patients.


Asunto(s)
Diabetes Mellitus/inducido químicamente , Diabetes Mellitus/epidemiología , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , Enfermedades Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Femenino , Humanos , Modelos Logísticos , Enfermedades Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
18.
Anticancer Res ; 41(6): 2885-2894, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34083279

RESUMEN

BACKGROUND/AIM: We evaluated the radiosensitizing effect of the combination treatment of trametinib, a MEK inhibitor, and temsirolimus, an mTOR inhibitor, on non-small-cell lung carcinoma (NSCLC) cells. MATERIALS AND METHODS: The effects of combining trametinib and temsirolimus with radiation in NSCLC cell lines were evaluated using clonogenic survival and apoptosis assays. DNA double-strand breaks and cell cycle distribution were analyzed using flow cytometry. Tumor volume was measured to determine the radiosensitivity in lung cancer xenograft models. RESULTS: Exposure of lung cancer cells to a combination of trametinib and temsirolimus reduced clonogenic survival and promoted radiation-induced apoptosis. Combined inhibition of MEK and mTOR induced prolonged expression of γH2AX after irradiation and resulted in prolonged G2/M cell cycle arrest after irradiation in A549 cells. In vivo studies revealed that co-administration of the drugs sensitizes lung cancer xenografts to radiotherapy. CONCLUSION: The combination of trametinib and temsirolimus can enhance lung cancer radiosensitivity in vitro and in vivo.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Quinasas Quinasa Quinasa PAM/metabolismo , Piridonas/farmacología , Pirimidinonas/farmacología , Tolerancia a Radiación/efectos de los fármacos , Sirolimus/análogos & derivados , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/patología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Daño del ADN , Quimioterapia Combinada , Humanos , Neoplasias Pulmonares/patología , Piridonas/administración & dosificación , Pirimidinonas/administración & dosificación , Transducción de Señal/efectos de los fármacos , Sirolimus/administración & dosificación , Sirolimus/farmacología , Células Tumorales Cultivadas
19.
Transl Cancer Res ; 10(12): 5204-5211, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35116370

RESUMEN

BACKGROUND: The incidence of second primary lung cancer (SPLC) is increasing with longer survival rates from breast cancer. Despite of studies to suggest the mutual exclusivity of epidermal growth factor receptor (EGFR) and human epidermal growth receptor 2 (HER2) in several cancers, the effect of HER2 expression in breast cancer on EGFR mutations in SPLC is unclear. Therefore, this study aimed to determine the association between HER2 expression and EGFR mutations. METHODS: We conducted a retrospective cohort study of breast cancer survivors diagnosed with SPLC after breast cancer treatment between 1997 and 2018. We investigated the association between HER2 expression in breast cancer and EGFR mutations in SPLC, specifically focusing on negative correlations by using logistic regression analysis. RESULTS: EGFR mutations in SPLC were detected in 19 of 38 patients. Analysis for HER2 revealed a statistically significant difference in the proportion of EGFR mutations between patients with SPLC and previous HER2 positive breast cancer (43.5%) and those with SPLC and previous HER2 negative breast cancer (90.0%; P=0.021). The ratio of EGFR mutations decreased with the degree of HER2 expression in patients with previous breast cancer (90.0%: for no HER2 expression, 62.5% for HER2 1+, 0.0% for HER2 2+, and 41.7% for HER2 3+; P=0.018). Multivariate logistic analyses revealed that EGFR mutations in SPLC were significantly associated with age [odds ratio (OR): 1.11, 95% confidence interval (CI): 1.01-0.23, P=0.039] and HER2 positive status (OR: 0.04, 95% CI: 0.01-0.56, P=0.017). CONCLUSIONS: This study suggests that the frequency of EGFR mutations in SPLC may be associated with low HER2 expression in previous breast cancer.

20.
Korean J Women Health Nurs ; 26(2): 109-119, 2020 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-36310574

RESUMEN

The purpose of this study was to describe prenatal nursing intervention studies on pregnant women and their families published in Korean nursing journals to identify research trends and to analyze the characteristics of intervention studies. This scoping review was conducted using Arksey and O'Malley's framework. We identified a research question and searched six domestic electronic databases for relevant articles. Forty-five references that met the inclusion and exclusion criteria were finally selected. We extracted the data using an analytic framework, and then collated and summarized the characteristics of the intervention studies. The most frequently used research designs were non-randomized controlled trials (91.1%), and only a few studies applied a specific theoretical framework (24.4%). The participants were mainly pregnant women only (64.4%) during the third trimester (35.6%) of pregnancy. Prenatal education was the most common type of intervention (48.9%), followed by complementary therapy (37.8%) and psychosocial support programs (13.3%). The most commonly used outcome variables were drawn from the psychological domain (44.5%), although distinct types of outcome variables-especially from the psychological and physical domains-were used to measure the effectiveness of different types of prenatal interventions. This review suggests that further prenatal nursing intervention studies in Korea should expand the study participants to include pregnant women's family members, high-risk and vulnerable groups, and women throughout entire pregnancy. Furthermore, it is necessary to develop integrative prenatal nursing interventions that promote family support and participation by facilitating partnerships among women, families, and nurses before, during, and after pregnancy.

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