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Chimeric antigen receptor (CAR) T-cell therapy is a promising therapeutic strategy against lymphoma. However, post-treatment relapses due to antigen loss remain a challenge. Here the authors designed a novel bicistronic CAR construct and tested its functions in vitro and in vivo. The CAR construct consisted of individual anti-CD19 and anti-CD20 single-chain fragment variables equipped with ICOS-CD3ζ and 4-1BB-CD3ζ intracellular domains, respectively. The CD19 and CD20 bicistronic CAR T cells exhibited tumor lytic capacities equivalent to corresponding monospecific CAR T cells. Moreover, when stimulated with CD19 and CD20 simultaneously, the bicistronic CAR T cells showed prolonged persistence and enhanced cytokine generation compared with single stimulations. Interestingly, the authors found that the 4-1BB signal was predominant in the signaling profiles of ICOS and 4-1BB doubly activated CAR T cells. In vivo study using a CD19/CD20 double-positive tumor model revealed that the bicistronic CAR T cells were more efficient than monospecific CD19 CAR T cells in eradicating tumors and prolonging mouse survival. The authors' novel bicistronic CD19/CD20 CAR T cells demonstrate improved anti-tumor efficacy in response to dual antigen stimulations. These data provide optimism that this novel bicistronic CAR construct can improve treatment outcomes in patients with relapsed/refractory B cell malignancy.
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Receptores de Antígenos Quiméricos , Animais , Antígenos CD19/genética , Humanos , Imunoterapia Adotiva , Proteína Coestimuladora de Linfócitos T Induzíveis/genética , Camundongos , Recidiva Local de Neoplasia , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos Quiméricos/genética , Linfócitos TRESUMO
The complete genomic sequence of a novel potyvirus from a noni plant in China (Morinda citrifolia) with foliar mosaic and chlorotic symptoms was determined. The genomic RNA consists of 9645 nucleotides (nt) excluding the poly(A) tail, containing the typical open reading frame (ORF) of potyviruses and encoding a large putative polyprotein of 3077 amino acids (aa). Pairwise comparisons showed that the virus shares 48.8%-58.5% sequence identity at the genome sequence level, and 38.5%-53.4% identity at the polyprotein sequence level with other members of the genus Potyvirus. Phylogenetic analysis indicated that the virus is most closely related to jasmine virus T and plum pox virus in the genus Potyvirus. These results suggest that this virus should be considered a distinct member of the genus Potyvirus, and it was tentatively named "noni mosaic virus" (NoMV).
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Morinda/virologia , Potyvirus/classificação , RNA Viral/genética , Tamanho do Genoma , Fases de Leitura Aberta , Filogenia , Potyvirus/genética , Potyvirus/isolamento & purificação , Análise de Sequência de RNA , Homologia de Sequência do Ácido NucleicoRESUMO
The photocatalytic decomposition of water to produce hydrogen is an important strategy to effectively utilize solar energy and solve the energy crisis. In this study, a highly efficient WP-nanoparticle-modified composite catalyst was successfully prepared. WP nanoparticles have been used as an efficient and acid-stable co-catalyst for the HER owing to their specific electronic structure, metalloid characteristics and catalytic activity. On the one hand, the octahedral spatial structure of UiO-66 not only provides attachment space for CdS and WP nanoparticles, but also effectively reduces the particle size and increases the dispersion of CdS and WP nanoparticles. On the other hand, the potential difference and the matching energy band positions of UiO-66 and CdS provide a feasible thermodynamic path for the transmission of photogenerated electrons. The intimate contact between the abovementioned three compounds resulted in a strong synergistic effect, which improved the efficiency of the photocatalytic H2 production. Under visible-light irradiation, the maximum H2 production in 5 h over the [UiO-66@CdS/WP (10 wt%)] photocatalyst was 395 µmol, which was 26.33 times that of pure CdS. The physical and chemical information of the samples could be obtained through XRD, SEM, TEM, XPS, BET and UV-vis DRS characterizations. Furthermore, based on the photoluminescence spectra, photoelectrochemical experiments and Mott-Schottky curves, we could reasonably explain the separation and transfer mechanisms of the photogenerated electrons and holes. The lower recombination rate of charge, enhanced intensity of light absorption, a short fluorescence lifetime (2.11 ns), a faster electron injection rate (KET = 2.32 × 108 s-1), a larger efficiency of electron injection (ηinj = 49.1%), high photocurrent response, and smaller charge transfer resistance accelerate the efficient separation and transfer of spatial charges, finally enhancing the photocatalytic performance.
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BACKGROUND: The objective of this study was to evaluate the feasibility and diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and (99m)Tc-methylenediphosphonate (MDP) whole-body bone scanning (BS) for the detection of osteolytic bone metastases. METHODS: Thirty-four patients with pathologically confirmed malignancies and suspected osteolytic bone metastases underwent 18F-FDG PET/CT and (99m)Tc-MDP whole-body BS within 30 days. The sensitivity, specificity, and accuracy with respect to the diagnosis of osteolytic bone metastases and bone lesions were compared between the two imaging methods. RESULTS: The sensitivity, specificity, and accuracy of 18F-FDG PET/CT for the diagnosis of osteolytic bone metastases were 94.3% (95% confidence interval [CI], 91.6-96.2%), 83.3% (95% CI, 43.6-96.9%), and 94.2% (95% CI, 91.5-96.1%), respectively. It was found that (99m)Tc-MDP whole-body BS could discriminate between patients with 50.2% (95% CI, 45.4-55.1%) sensitivity, 50.0% (95% CI, 18.8-81.2%) specificity, and 50.2% (95% CI, 45.5-55.1%) accuracy. 18F-FDG PET/CT achieved higher sensitivity, specificity, and accuracy in detecting osteolytic bone metastases than 99mTc-MDP whole-body BS (p<0.001). CONCLUSIONS: F-FDG PET/CT has a higher diagnostic value than (99m)Tc-MDP whole-body BS in the detection of osteolytic bone metastases, especially in the vertebra.
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Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/secundário , Fluordesoxiglucose F18 , Osteólise/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Medronato de Tecnécio Tc 99m , Adulto , Idoso , Neoplasias Ósseas/complicações , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteólise/etiologia , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos , Imagem Corporal Total/métodosRESUMO
Vascular endothelial growth factor-A (VEGF-A) plays a critical role in physiologic and pathologic angiogenesis through its receptors especially through VEGFR2. The lack of cross-reactivity of monoclonal antibodies with human VEGFR2/mouse Flk-1 is a major obstacle in preclinical developments. In this study, using a unique hybridoma technique, we generated a panel of 30 neutralization anti-VEGFR2 rabbit monoclonal antibodies (RabMAbs) either blocking VEGF/VEGFR2 interaction or inhibiting VEGF-stimulated VEGFR2 tyrosine kinase phosphorylation. Among 18 RabMAbs with human/mouse VEGFR2 cross-reactivity, we humanized one lead candidate RabMAb by Mutational Lineage Guided (MLG) method and further demonstrated its potent inhibition of tumor growth in xenograft mouse model. Our study suggests that RabMAbs are highly relevant for therapeutic applications.
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Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/farmacologia , Afinidade de Anticorpos , Especificidade de Anticorpos , Antineoplásicos/administração & dosagem , Reações Cruzadas , Feminino , Células HEK293 , Humanos , Hibridomas/imunologia , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Dados de Sequência Molecular , Neovascularização Patológica/imunologia , Neovascularização Patológica/terapia , Fosforilação , Ligação Proteica , Mapeamento de Interação de Proteínas , Coelhos , Fator A de Crescimento do Endotélio Vascular/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Epiverta chelonia (Mader 1933; Coleoptera: Coccinellidae) is an important economically and scientifically valuable insect. In this study, the first complete mitochondrial genome of E. chelonia was sequenced and characterized using next-generation sequencing techniques. The circular mitogenome of E. chelonia consists of 17,347 bp including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and a control region (D-loop). The base composition was AT-biased (75.77%). Bayesian Inference and Maximum likelihood phylogenetic trees strongly supported the monophyly of Coccinellinae. Also, E. chelonia was supported as the sister group of Subcoccinella vigintiquatuorpunctata, within Epilachninae. Thus, the E. chelonia mitochondrial genome will be a fundamental resource for understanding the molecular phylogenetic relationships of the species-rich family Coccinellidae of Coleoptera.
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Krukenberg tumor refers to a malignancy in the ovary that metastasizes from a primary site, classically the gastrointestinal tract. Pregnancy complicated with a Krukenberg tumor is very rare. In this report, we present two unusual cases of pregnant women with Krukenberg tumors of gastric origin. One case was a full-term pregnant woman with preeclampsia (PE) who underwent a caesarean section when bilateral enlarged ovaries were incidentally identified. Histopathology of the wedge resection biopsy showed single-ring cell carcinoma; this was followed by gastroscopy, which indicated a gastric origin. The woman received chemotherapy but died 6 months later. Another case was a pregnant woman at 30 gestational weeks with abdominal pain complicated with early-onset PE. Ultrasonography and magnetic resonance imaging showed bilateral enlarged ovaries and elevated tumor markers. Gastroscopy indicated linitis plastica. After an emergency caesarean section, adnexectomy was performed, and postoperative histopathology confirmed a Krukenberg tumor. The woman died 2 months after delivery. Gastrointestinal symptoms during pregnancy may indicate a malignancy of rare gastrointestinal origin. PE complicated with Krukenberg tumors in pregnancy should be considered in future studies.
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Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation with live Lactobacillus may benefit the recovery of BV, however, the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin Lactobacillus with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent Scores ≥ 7 and < 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (72.73% and 84.00% at day 14, 57.14% and 60.00% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent Scores < 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the intestinal microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that L. gasseri TM13 and L. crispatus LG55 mainly acted through the intestine. A higher abundance of Prevotella timonensis at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up, L. gasseri TM13 and L. crispatus LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to restore the vaginal health of patients recovering from BV. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.
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Lactobacillus crispatus , Lactobacillus gasseri , Vaginose Bacteriana , Feminino , Humanos , Adjuvantes Imunológicos/uso terapêutico , Adjuvantes Farmacêuticos , Lactobacillus/fisiologia , Metronidazol/uso terapêutico , Resultado do Tratamento , Vagina/microbiologia , Vaginose Bacteriana/microbiologiaRESUMO
Illeis bistigmosa (Mulsant, 1850) is a potential biological control agent of powdery mildews. We have determined the first mitochondrial genome of I. bistigmosa. The circular mitogenome of I. bistigmosa consists of 17,840 bp including 13 protein-coding genes, 22 tRNAs, 2 rRNAs, and a control region (D-loop). The base composition was AT-biased (78.44%). Maximum-likelihood phylogenetic trees strongly supported the monophyly of Coccinellinae. Illeis bistigmosa is the sister group of Halyzia sedecimguttata and Halyziini species (unclassified Halyziini), within fungivorous coccinellids. Illeis bistigmosa mitochondrial genome will be a fundamental resource for understanding the molecular phylogenetic relationships of the species-rich family Coccinellidae of Coleoptera.
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Tuvans are mainly distributed in Siberia (the Republic of Tuva), Mongolia, and China. The genetic origin of Chinese Tuvans remains controversial. The Tuvans in China were classified as Mongolians in the early 1950s by the National Ethnic Affairs Commission of China, but they defined themselves as a separate group. To resolve this dispute and determine their genetic relationships with the peoples in Central Asia, we randomly selected 150 male subjects from the Tuvans in the Altai region of Xinjiang Uygur Autonomous Region in China. Fourteen Y chromosomal markers were genotyped using the RFLP method or direct sequencing. These haplogroup data were combined with public data for 15 populations in South Siberia and Central Asia. Tuvans in both China and the Republic of Tuva had the highest frequencies of haplogroups K-M9 and Q-M242. Principal component analysis demonstrated that the Tuvans in China were of a distinct cluster, separated from their neighbors, the Mongolians and Kazakhs, which finding was consistent with the Analysis of Molecular Variances. Further population tree analysis revealed that Tuvans were on a far-separated cluster from their neighbors. Based on these results, we propose that the Tuvans (in both China and the Republic of Tuva) constitute a group distinct from Mongolians and from other Central Asia populations. However, the genetic results might be the consequence of some evolutionary forces like genetic drift and founder effect, and do not necessarily reflect their ultimate origin.
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Povo Asiático/genética , Cromossomos Humanos Y , Haplótipos/genética , Epidemiologia Molecular , Adolescente , Adulto , Idoso , Análise de Variância , Criança , China/etnologia , Análise por Conglomerados , Genética Populacional , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Análise de Componente Principal , Sibéria/etnologia , MigrantesRESUMO
The purpose of this study was to evaluate the effectiveness of metronidazole and oral probiotics adjunct to metronidazole in the treatment of bacterial vaginosis (BV). One hundred and twenty-six Chinese women with BV were enrolled in this parallel, controlled trial, and were randomly assigned into two study arms: the metronidazole group, which was prescribed metronidazole vaginal suppositories for 7 days, and the adjunctive probiotic group, which received Lacticaseibacillus rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 orally for 30 days as an adjunct to metronidazole. Clinical symptoms and Nugent scores at the initial visit, 30 days and 90 days were compared. There was no significant difference of the 30-day total cure rate between the adjunctive probiotic group (57.69%) and the metronidazole group (59.57%), with an odds ratio (OR) of 0.97 (95% confidence interval (CI), 0.70 to 1.35, p-value = 0.04), or of the 90-day total cure rate (36.54% vs. 48.94%, OR, 0.75; 95% CI, 0.47 to 1.19; p-value = 0.213). Also, no significant difference of the vaginal and faecal microbial diversity and structure between the two groups at 0, 30 or 90 days were shown based on 16S rRNA sequences. The probiotic species were rarely detected in either the vaginal microbiota or the faecal microbiota after administration which may revealed the cause of noneffective of oral probiotics. No serious adverse effects were reported in the trial. The study indicated that oral probiotic adjunctive treatment did not increase the cure rate of Chinese BV patients compared to metronidazole.
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Probióticos , Vaginose Bacteriana , China , Feminino , Humanos , Probióticos/uso terapêutico , Estudos Prospectivos , RNA Ribossômico 16S , Resultado do Tratamento , Vagina , Vaginose Bacteriana/tratamento farmacológicoRESUMO
In the Hanasi scenic spot of the Altai Region, Xinjiang Uygur Autonomous Region, China, there is a special population known as Xinjiang Tuvinians for short. These Tuvinians were classified as Mongolians in the early 1950s by the National Ethnic Affairs Commission of China, but they claimed that they have an independent origin. To resolve this dispute and their genetic relationships with the people in the neighboring regions, we randomly selected 150 male Tuvinians in the Altai Region. Fourteen Y chromosomal markers were genotyped and eleven haplogroups were constructed. The frequencies of the haplogroups K-M9 and Q-M242 were higher in Xinjiang Tuvinians or Tuvinians in the Tuva Republic than those in the other populations (e.g., Mongolians and Kazakh). Principal component analysis , multi-dimensional scaling analysis and further phylogenetic tree analysis revealed that the Xinjiang Tuvinians were far separated from Mongolians and Kazakh. Based on these results, we proposed that Xinjiang Tuvinians are genetically distinct from Mongolians and Kazakh.
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Genética Populacional , Grupos Raciais/genética , China/etnologia , Cromossomos Humanos Y/genética , Humanos , Masculino , Filogenia , Grupos Raciais/classificação , Grupos Raciais/etnologiaRESUMO
The abundant transition metal phosphides co-catalysts on the earth can satisfy the sustainable and clean solar H2 production through photocatalytic water splitting, which is promising to replace the rare precious metals, such as Pt, Au, Pd, Ru and so on. In this paper, we use the temperature-programmed solid phase method to prepare WP nanoparticles. Based on the Density Functional Theory (DFT) calculations, we demonstrate that the WP nanoparticles possess outstanding electrical conductivity and excellent capability to transport electrons. WP nanoparticles are loaded onto the surface of UiO-66 via the ultrasound-assisted impregnation method to induce a highly efficient visible-light photocatalytic H2 production activity of 384⯵mol in 5â¯h, which is 10.67 times than that of pure UiO-66. The catalytic performance is attributed to the excellent metallic conductivity and the favourable Fermi level position of WP nanoparticles. Further studies of PL, TRPL and Mott-Schottky curves, we can not only know that the modification of WP nanoparticles do improve the electron transfer ability, but also that the matched work functions between the EY and UiO-66 provides a feasible thermodynamic path for the transmission of electrons. Our work demonstrates that the earth-abundant transition metal phosphides material have the potential to construct cheaper and high catalytic performance photocatalysts.
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In terms of energy acquisition, research on the photocatalytic cracking of water to produce hydrogen has become a hub for us to make a transition from theoretical research to practical applications. Charge separations and surface redox reactions of semiconductors are key factors that affect hydrogen production activity. In this study, we used an n-type semiconductor WP as a cocatalyst to modify the solid solution of ZnxCd1-xS and found it to have excellent photocatalytic activity under visible light irradiation. Ultraviolet diffuse reflectance spectroscopy showed the red shift of the absorption band of the composite catalyst and the strong absorption of visible light. Under the action of the matching energy band structure, the fluorescence lifetime of the composite catalyst is shortened (2.33 ns) and the electron injection rate is accelerated (Ket = 0.58 × 109 s-1). Under these favorable conditions, the increased hydrogen production activity of the composite catalyst is finally reflected in the enhanced hydrogen production rate, which reached up to 15 028.6 µmol g-1 h-1. In addition, the yield of hydrogen produced by adding a fresh lactic acid catalyst in the fifth cycle after four cycles of testing was greatly improved. Obviously, the addition of WP turns the composite catalyst into a photocatalyst with high efficiency, stability and is a non-noble metal cocatalyst. Finally, through a series of characterization experiments (SEM, TEM, XPS, BET, Mott-Schottky et al.), we proposed the possible mechanism of WP/ZnxCd1-xS that efficiently promotes hydrogen production. This provides new understanding for designing an effective cocatalyst modified semiconductor to improve photocatalytic activity.
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The separation and transfer of photoelectrons is a crucial factor in the process of photocatalysis. Herein, we successfully designed and prepared WP as a cocatalyst, modified the g-C3N4(CN)/CdS heterojunction structure, achieved the effective separation and directional transfer of photoelectrons, and also efficient photocatalytic hydrogen evolution. In addition, the as-prepared WP-CN/CdS composite photocatalyst not only prominently improved the separation and pre-assigned transfer of photogenerated electrons, but also had abundant surface active sites, which greatly improved the photocatalytic performance of the catalyst; namely, the highest photocatalytic activity of WP-CN/CdS was achieved at 5% WP content and the highest hydrogen production rate could reach 18 238.89 µmol h-1 g-1, which is about 12.49 times that of pure CdS. The detailed characterization studies with SEM, TEM, XRD, XPS, DRS, UV-vis, BET, transient photocurrent, FT-IR etc. effectively supported the abovementioned results, and all the characterization results were in good agreement with each other. Moreover, a possible mechanism of the photocatalytic reaction in the WP-CN/CdS system is proposed.
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Transfusão Feto-Fetal , Cardiopatias Congênitas , Gêmeos Unidos , Gravidez , Feminino , Humanos , Gêmeos Unidos/cirurgiaRESUMO
Harvesting and charge management is obtained by means of Ni4S3 modified Metal-organic Frameworks (MOF) and rGO, namely, the Uio-66 (Zr)/rGO combined with Ni4S3 photocatalyst was successfully prepared with the solvothermal method. The Ni4S3 acted as the electron transfer agent greatly improve the electrons transmission from the excited state dye to the rGO/MOF surface for proton reduction reaction. The hydrogen production amount over EY-sensitized rGO/MOF/Ni4S3 photocatalyst has reached 280⯵mol for 5â¯h, which is about 14 times than that of the pure Ni4S3 photocatalyst and 185 times than that of the pure rGO/MOF photocatalyst under visible light irradiation (λâ¯≥â¯420â¯nm). In the composite, the rGO acts as electron-transfer mediator and Ni4S3 serves as H2-evolution active site. A series of studies shown that the Ni4S3 modified MOF and rGO provided more active sites and improved the efficiency of photo-generated charge separation by means of several characterizations such as SEM, XRD, XPS, Element Mapping, UV-vis DRS, BET, Photocurrent, Voltammetric Scanning, Fluorescence Spectra and FTIR. and the results of which were in good agreement with each other. The photoelectron migration rate and photogenerated charge separation efficiency of the composite can be obviously increased with graphene as a good electron acceptor and transfer medium and Ni4S3 as hydrogen producing active site.
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A high-efficiency Ni-MOF-74/CdS/Co3O4 composite catalyst, the CdS co-boosting with Ni-MOF-74 and Co3O4, is successfully prepared. The maximum amount of hydrogen evolution reaches about 581 µmol for 5 h over the Ni-MOF-74/CdS/Co3O4 (10 wt% Co) photocatalyst under visible light irradiation, which is 16.2 times higher than that over pure CdS. The detailed physical and chemical inner mechanism of the Ni-MOF-74/CdS/Co3O4 composite catalyst is investigated by means of XRD, SEM, TEM, XPS, BET, UV-visible DRS etc. In the most valuable aspect, we investigate the photoelectron and hole transfer mechanism by photoluminescence spectroscopy, excited state electron decay, and photoelectrochemical experiments. The results show that the lower electron and hole pair recombination, larger electron transfer rate constant (KET = 0.2 × 109 s-1), larger electron injection efficiency (ηinj = 44.7%), smaller carrier charge resistance in the semiconductor film (Rfilm = 3523 Ω cm2), and smaller charge transfer and reaction resistance at the interface between the semiconductor and the electrolyte (Rct = 1.96 Ω cm2) together accelerate the charge separation and transfer, thereby enhancing photocatalytic performance.
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AuroraA, a mitotic kinase, is reported to be amplified and overexpressed in a variety of human tumors. Active mutants of AuroraA can transform mouse fibroblasts and form tumors in nude mice. However, the mechanism behind this oncogenic potential remains elusive. In this study, we investigated the consequences of AuroraA overexpression and showed that increased AuroraA levels compromise the mitotic spindle checkpoint triggered by nocodazole, a microtubule polymerization inhibitor. This is accomplished by disrupting the proper assembly of the mitotic checkpoint complex at the level of the Cdc20-BubR1 interaction. As a result, the spindle checkpoint complex fails to form and cells progress through mitosis without proper arrest in response to nocodazole. This ability to override the mitotic spindle checkpoint was found to be independent of AuroraA kinase activity. We conclude that maintenance of a functional balance between AuroraA and mitotic checkpoint proteins is essential for the proper progression through mitosis. This study therefore offers a possible explanation of how deregulation of AuroraA can contribute to genetic instability and tumorigenesis.
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Microtúbulos/efeitos dos fármacos , Nocodazol/farmacologia , Proteínas Quinases/metabolismo , Fuso Acromático , Aurora Quinases , Proteínas de Ciclo Celular , Linhagem Celular , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Humanos , Proteínas Serina-Treonina Quinases , Proteínas de XenopusRESUMO
OBJECTIVE: The objective of this study was to explore the effects of hypotonic and isotonic oral mannitol on intestinal distention and fluorine-18 fluorodeoxyglucose ((18)F-FDG) intake in PET/computed tomography (CT) imaging. MATERIALS AND METHODS: A total of 124 patients without gastrointestinal disease were evaluated with PET/CT imaging and divided into four groups using a random number table. Group 1 drank plain water, group 2 drank 2.5% mannitol, group 3 drank 2.5% mannitol and also received 10 mg of scopolamine butylbromide, and group 4 drank 2.5% mannitol and also received 20 mg of scopolamine butylbromide. The patients in each group underwent PET/CT imaging 50 min after (18)F-FDG injection. In these groups, differences such as age, sex, disease distribution, oral liquid amount, and adverse reactions were compared. Gastrointestinal distention and F-FDG intake were analyzed by two experts in nuclear medicine by visual observation. Data were statistically analyzed using a rank-sum test, R×C contingency table, one-way analysis of variance, and a paired t-test. RESULTS: There were no significant differences in blood glucose levels after oral administration of 2.5% mannitol (t=0.62, P>0.05). Gastrointestinal distention of patients in groups 2, 3, and 4 was superior to that of patients in group 1 (P<0.05/6). In addition to the sigmoid colon and rectum, (18)F-FDG intake in each part of the gastrointestinal tract in groups 2, 3, and 4 was less than that in group 1 (P<0.05/6). Patients in group 4 experienced significantly more adverse reactions compared with patients in the other groups (P<0.05). CONCLUSION: Oral negative contrast agent and hypotonic bowel preparation decreased the physiological intake of (18)F-FDG, increased the distention of the gastrointestinal tract, and thus improved the image quality.