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Piezochromic materials that exhibit pressure-dependent luminescence variations are attracting interest with wide potential applications in mechanical sensors, anticounterfeiting and storage devices. Crystalline porous materials (CPMs) have been widely studied in piezochromism for highly tunable luminescence. Nevertheless, reversible and high-contrast emission response with a wide pressure range is still challenging. Herein, the first example of hierarchical porous cage-based πOF (Cage-πOF-1) with spring structure was synthesized by using aromatic chiral cages as building blocks. Its elastic properties evaluated based on the bulk modulus (9.5â GPa) is softer than most reported CPMs and the collapse point (20.0â GPa) significantly exceeds ever reported CPMs. As smart materials, Cage-πOF-1 displays linear pressure-dependent emission and achieves a high-contrast emission difference up to 154â nm. Pressure-responsive limit is up to 16â GPa, outperforming the CPMs reported so far. Dedicated experiments and density functional theory (DFT) calculations illustrate that π-π interactions-dominated controllable structural shrinkage and porous-spring-structure-mediated elasticity is responsible for the outstanding piezofluorochromism.
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Chiral induction has been an important topic in chemistry, not only for its relevance in understanding the mysterious phenomenon of spontaneous symmetry breaking in nature but also due to its critical implications in medicine and the chiral industry. The induced chirality of fullerenes by host-guest interactions has been rarely reported, mainly attributed to their chiral resistance from high symmetry and challenges in their accessibility. Herein, we report two new pairs of chiral porous aromatic cages (PAC), R-PAC-2, S-PAC-2 (with Br substituents) and R-PAC-3, S-PAC-3 (with CH3 substituents) enantiomers. PAC-2, rather than PAC-3, achieves fullerene encapsulation and selective binding of C70 over C60 in fullerene carbon soot. More significantly, the occurrence of chiral induction between R-PAC-2, S-PAC-2 and fullerenes is confirmed by single-crystal X-ray diffraction and the intense CD signal within the absorption region of fullerenes. DFT calculations reveal the contribution of electrostatic effects originating from face-to-face arene-fullerene interactions dominate C70 selectivity and elucidate the substituent effect on fullerene encapsulation. The disturbance from the differential interactions between fullerene and surrounding chiral cages on the intrinsic highly symmetric electronic structure of fullerene could be the primary reason accounting for the induced chirality of fullerene.
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Conversion of curtilage land into cropland or grassland can have substantial effects on soil nutrition and microbial activities; however, these effects remain ambiguous. This is the first study to compare the soil organic carbon (SOC) fractions and bacterial communities in rural curtilage, converted cropland, and grassland compared with cropland and grassland. This study determined the light fraction (LF) and heavy fraction (HF) of organic carbon (OC), dissolved organic carbon (DOC), microbial biomass carbon (MBC), and the microbial community structure by conducting a high-throughput analysis. Curtilage soil had significantly lower OC content, the DOC, MBC, LFOC and HFOC of grassland and cropland soils were 104.11%, 55.58%, 264.17%, and 51.04% higher than curtilage soil averagely. Cropland showed notably high bacterial richness and diversity, with Proteobacteria (35.18%), Actinobacteria (31.48%), and Chloroflexi (17.39%) predominating in cropland, grassland, and curtilage soil, respectively. Moreover, DOC and LFOC contents of converted cropland and grassland soils were 47.17% and 148.65% higher than curtilage soil while MBC content was 46.24% lower than curtilage soil averagely. Land conversion showed more significant effects on microbial composition than land-use differences. The abundant Actinobacteria and Micrococcaceae population and the low MBC contents indicated a "hungry" bacterial state in the converted soil, whereas the high MBC content, Acidobacteria proportion, and relative abundance of functional genes in the fatty acid and lipid biosynthesis indicated a "fat" bacterial state in cropland. This study contributes to the improvement of soil fertility and the comprehension and efficient use of curtilage soil.
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Carbono , Suelo , Suelo/química , Carbono/análisis , Agricultura , Bacterias/genética , Biomasa , ChinaRESUMEN
To better understand the etiology of papillary thyroid carcinoma, we did next-generation sequencing for the exomes and transcriptomes of a Chinese cohort of 28 pairs of DNA and RNA samples extracted from papillary thyroid carcinoma tumors and adjacent normal thyroid samples. The Chinese papillary thyroid carcinoma tumors harbored somatic mutations in the known driver genes, such as KRAS, TP53, BRAF, ERBB2 , and MET . In addition, we identified novel papillary thyroid carcinoma candidate genes that had not been well studied before. We also identified a gene mutation signature involving SPTA1, MAP2, SYNE1 , and SLIT3 that is significantly associated with survival of papillary thyroid carcinoma patients. Transcriptome analysis using the initial papillary thyroid carcinoma tumor samples and a new Chinese papillary thyroid carcinoma dataset identified six commonly upregulated oncogenic pathways in both datasets including eukaryotic translation initiation factor 2, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/serine/threonine kinase (AKT), Ephrin Receptor, Rho Family GTPase signaling, nuclear factor, erythroid 2 like 2 (NRF2)-mediated oxidative stress response, and remodeling of epithelial adherens junctions. Overall, we identified novel candidate genes and oncogenic pathways important to the etiology of papillary thyroid carcinoma in Chinese patients and found the association of a gene signature with the survival outcome of the thyroid cancer patients. These findings may help in moving toward the more comprehensive and effective personalized treatment of papillary thyroid carcinoma in Chinese.
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Pueblos del Este de Asia , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Mutación , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
The synthesis of ultra-stable chiral porous organic cages (POCs) and their controllable chiral self-sorting at the molecular and supramolecular level remains challening. Herein, we report the design and synthesis of a serial of axially chiral porous aromatic cages (PAC 1-S and 1-R) with high chemical stability. The theoretical and experimental studies on the chiral self-sorting reveal that the exclusive self-recognition on cage formation is an enthalpy-driven process while the chiral narcissistic and self-sorting on supramolecular assembly of racemic cages can be precisely regulated by π-π and C-H π interactions from different solvents. Regarding the chemical stability, the crystallinity of PAC 1 is maintained in aqueous solvents, such as boiling water, high-concentrated acid and alkali; mixtures of solvents, such as 1 M H2SO4/MeOH/H2O solution, are also tolerated. Investigations on the chiral sensing performance show that PAC 1 enables enantioselective recognition of axially chiral biaryl molecules.
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Heparanase (HPSE) is an endo-ß-D-glucuronidase overexpressed in different types of human cancer, and a predicted target of microRNA (miRNA/miR)-219a-2-3p in thyroid cancer. The present study aimed to investigate the potential role of HPSE and miR-219a-2-3p in thyroid cancer, and the molecular mechanism of miR-219a-2-3p regulating the proliferation of thyroid cancer cells via HPSE was confirmed. Immunohistochemistry analysis was performed to detect HPSE expression in thyroid cancer sections. In addition, reverse transcription-quantitative PCR analysis was performed to detect mRNA and miR-219a-2-3p expression levels in thyroid cancer samples and cell lines. miR-219-2-3p mimic or HPSE plasmid were transfected into B-CPAP and TPC-1 thyroid cancer cells. Furthermore, western blot analysis was performed to detect the protein expression levels of HPSE and cyclin D1. Cell cycle analysis was performed using propidium iodide staining and flow cytometry, and EdU incorporation was performed to detect cell proliferation. The results demonstrated that high HPSE expression was significantly associated with tumor size, extracapsular invasion and lymph node metastasis. Notably, a statistically negative correlation was observed between HPSE mRNA expression and miR-219a-2-3p expression in thyroid cancer tumors, as well as in thyroid cancer cell lines. When exogenously expressed in B-CPAP and TPC-1 cells, miR-219a-2-3p induced cell cycle arrest at the G0/G1 phase and decreased the percentage of proliferating cells. Furthermore, HPSE and cyclin D1 protein expression decreased following transfection with miR-219a-2-3p. Notably, when HPSE was ectopically expressed in miR-219a-2-3p transfected cells, cyclin D1 expression and the number of proliferative cells increased. Taken together, these results suggest that HPSE contributes to the proliferation of thyroid cancer cells. In addition, miR-219a-2-3p was confirmed to target HPSE and inhibit cell proliferation, which was associated with cyclin D1 suppression-mediated cell cycle arrest.
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Alpha-fetoprotein (AFP) is one of the most important biomarkers associated with primary liver cancer, and the main approaches for diagnosis are based on immunoassay. Affibody is a 58 amino acids peptide derived from the Z domain of staphylococcal protein A and generally applied in imaging diagnosis, clinical therapeutics and biotechnology research. The aim of this study was therefore to develop a novel affibody-based ELISA for detection of AFP. After three rounds of biopanning, six AFP-binding affibody peptides were selected using phage display technology, among them affibody ZAFPD2 showed high and specific binding affinity to AFP. An affibody dimer of ZAFPD2 was created, named (ZAFP D2)2, expressed in E.coli and the purified (ZAFP D2)2 recombinant protein showed higher binding affinity to AFP, as well as high thermal stability. A novel affibody-based two-site ELISA method using ZAFPD2 or (ZAFP D2)2 and polyclonal antibody to detect AFP was developed, the detection limit of the immunoassay using (ZAFP D2)2 was 2 ng mL-1 that was 4 times lower than ZAFPD2, which meets the requirements for practical application. Therefore, this concept of affibody-based ELISA may provide a new method for the detection of various cancer biomarkers.
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Anticuerpos/inmunología , Biblioteca de Péptidos , alfa-Fetoproteínas/inmunología , Anticuerpos/química , Sitios de Unión , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Unión Proteica , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/metabolismo , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/metabolismoRESUMEN
Natural killer (NK) cells are potent cytotoxic effector cells of the innate immune system and play an important role in tumor immunosurveillance and control. NKG2D is an activating receptor of NK cells. The NKG2D receptor-ligand system has contributed to immune cells recognizing tumor cells and the tumor microenvironment. In order to stretch the application of NK cells on adoptive immunotherapy for B-cell malignancies, we designed and produced a novel bispecific ULBP1×CD19-scFv fusion protein, in which the extracellular domain of NKG2D ligand ULBP1 was fused to a single chain variable fragment (scFv) of anti-CD19. The vector expressing ULBP1×CD19-scFv protein was constructed and expressed in Pichia pastoris. Effects of medium composition, concentration of methanol as the inducer, induction time and broth content in shake flask on the expression of the recombinant protein were investigated. The results showed that the optimized conditions for ULBP1×CD19-scFv expression were 1% methanol induction for 96 h with 15% broth content. The secreted recombinant protein was purified using ammonium sulfate fractionation and Ni-NTA affinity chromatography and the purity is about 93%. The cytotoxicity of NK92-MI cells against CD19+ Raji cells was enhanced in the presence of purified ULBP1×CD19-scFv protein. These results indicated that ULBP1 could be used as an activating element of bispecific killer engagers (BiKEs) and Pichia pastoris yeast might be an alternative expression host for BiKEs production.
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Anticuerpos Biespecíficos , Antígenos CD19/inmunología , Células Asesinas Naturales/inmunología , Activación de Linfocitos , Subfamilia K de Receptores Similares a Lectina de Células NK , Anticuerpos de Cadena Única , Anticuerpos Biespecíficos/química , Anticuerpos Biespecíficos/inmunología , Anticuerpos Biespecíficos/aislamiento & purificación , Células Hep G2 , Humanos , Subfamilia K de Receptores Similares a Lectina de Células NK/antagonistas & inhibidores , Subfamilia K de Receptores Similares a Lectina de Células NK/inmunología , Proteínas Recombinantes de Fusión , Anticuerpos de Cadena Única/química , Anticuerpos de Cadena Única/inmunología , Anticuerpos de Cadena Única/aislamiento & purificaciónRESUMEN
Two new aggregation-induced emission (AIE)-active cyclemetalated cationic Ir(iii) complexes have been rationally designed and synthesized by introducing O-H substituents into Schiff base ligands. π-Hydrogen bonding is successfully exploited for the first time to realize the mechanochromic luminescence (MCL) property by the synergistic effect of O-H and F substituents in complex 1. An X-ray crystal structure analysis of the two complexes suggests that the intramolecular hydrogen bonding effectively restricted the molecular motions, thus causing typical AIE characteristics. More importantly, a loosely packed structure constructed from intermolecular hydrogen bonding interactions (O-Hπ and C-HF) is obtained, and it is susceptible to mechanical stimulation. Powder X-ray diffraction (PXRD) studies also prove that the MCL behavior of complex 1 is caused by the reversible phase transition from crystalline to amorphous state under grinding and solvent recrystallization, leading to a change in emission colors. A re-writable phosphorescence data recording device was fabricated using complex 1 as the active material. Our molecular design strategies provide a new avenue for achieving efficient phosphorescence materials with AIE and MCL properties.
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The chemical looping process is promising for CO2 conversion because of the much higher CO2 conversion efficiency than the photocatalytic and electrocatalytic processes. Conventional oxygen carriers have to include a high content of inert support, typically Al2O3, to avoid sintering, thus leading to a trade-off between reactivity and stability. Here, we propose the use of ion-conductive GdxCe2-xO2-δ (GDC) to prepare the supported oxygen carriers. The resulting Fe2O3/GDC materials achieve both high reactivity and stability. Fe2O3/Gd0.3Ce1.7O2-δ shows high CO productivity (â¼10.79 mmol·g-1) and CO production rate (â¼0.77 mmol·g-1·min-1), which are twofold higher than that of Fe2O3/Al2O3. The performance remains stable even after 30 cycles. The mechanism study confirmed the rate-limiting role of the oxygen-ion conductivity, and the GDC support enhanced the oxygen-ion conductivity of oxygen carriers during the redox reactions, thus leading to improved CO2 splitting performance. A roughly linear relationship between the oxygen-ion conductivity and CO2 yield is also obtained and verified in our testing conditions. This relation can be used to predict and select oxygen carriers with high CO2 splitting performance.
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Dióxido de Carbono , Oxígeno , Oxidación-ReducciónRESUMEN
INTRODUCTION: Sineoculis homeobox homolog 1 (Six1) overexpression has been implicated in several human cancers. To date, its clinical significance and potential function in human thyroid cancer remain unclear. METHODS: Immunohistochemistry was used to examine the protein expression of BCAT1 in 89 cases of thyroid cancer tissues. We overexpressed and knockdown Six1 in TPC-1 and B-CPAP thyroid cancer cell lines. Biological roles and potential mechanisms of Six1 were examined using CCK-8, colony formation assay, Matrigel invasion assay, Western blot, PCR, ATP assay, and 2-NBDG uptake assay. RESULTS: We showed that Six1 protein was upregulated in thyroid cancers and was associated with tumor size and nodal metastasis. Analysis of TCGA dataset indicated that Six1 mRNA was higher in thyroid cancers compared with normal thyroid. CCK-8, colony formation and Matrigel invasion assays demonstrated that Six1 overexpression promoted proliferation, colony number and invasion while Six1 siRNA knockdown inhibited the growth rate, colony formation ability and invasive ability in both cell lines. Notably, Six1 upregulated glucose consumption, lactate production level and ATP level. 2-NBDG uptake analysis showed that Six1 overexpression upregulated glucose uptake while Six1 knockdown inhibited glucose uptake. Further analysis revealed that Six1 overexpression upregulated Snail, MMP2 and GLUT3 at both mRNA and protein levels. TCGA analysis demonstrated positive associations between Six1 and Snail, MMP2 and GLUT3 at the mRNA levels. CONCLUSION: Taken together, our data demonstrated that Six1 was upregulated in human thyroid cancers and promoted cell proliferation and invasion. Our data also revealed new roles of Six1 in thyroid cancer development by modulating glucose metabolism and invasion, possibly through regulation of Snail, MMP2 and GLUT3.
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To characterize the somatic alterations of papillary thyroid carcinomas (PTC) in Chinese patients, we performed the next-generation-sequencing (NGS) study of the tumor-normal pairs of DNA and RNA samples extracted from 16 Chinese PTC patients. The whole genome sequencing (WGS) and transcriptome sequencing (RNA-seq) were conducted for 6 patients who were either current or former smokers and the whole exome sequencing (WES) and RNA-seq were conducted for another 10 patients who were never smokers. The NGS data were analyzed to identify somatic alteration events that may underlie PTC in Chinese patients. We identified a number of PTC driver genes harboring somatic driver mutations with significant functional impact such as COL11A1, TP53, PLXNA4, UBA1, AHNAK, CSMD2 and TTLL5 etc. Significant driver pathways underlying PTC were found, namely, the metabolic pathway, the pathway in cancer, the olfactory transduction pathway and the calcium signaling pathway. In addition, this study revealed genes with significant somatic copy number aberrations and corresponding somatic gene expression changes in PTC tumors, the most promising ones being BRD9, TRIP13, FZD3, and TFDP1 etc. We also identified several structural variants of PTCs, especially the novel in-frame fusion proteins such as TRNAU1AP-RCC1, RAB3GAP1-R3HDM1, and ENAH-ZSWIM5. Our study provided a list of novel PTC candidate genes with somatic alterations that may function as biomarkers for PTC in Chinese patients. The follow-up mechanism studies may be conducted based on the findings from this study.
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Biomarcadores de Tumor/genética , Mutación , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , ATPasas Asociadas con Actividades Celulares Diversas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteínas de Ciclo Celular/genética , China/epidemiología , Colágeno Tipo XI/genética , Biología Computacional/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia de ARN/métodos , Cáncer Papilar Tiroideo/epidemiología , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/patología , Factores de Transcripción/genética , Proteína p53 Supresora de Tumor/genética , Secuenciación del Exoma/métodos , Secuenciación Completa del Genoma/métodos , Adulto JovenRESUMEN
An affibody is a 58 amino acids peptide derived from the Z domain of staphylococcal protein A and generally applied in areas such as imaging diagnosis, clinical therapeutics and biotechnology research. To screen for an affibody targeting the immune checkpoint PD-L1, a combinatorial affibody library was generated in yeast using degenerate overlap PCR primers and In-fusion technology. Z-j1 and Z-j2 affibodies targeting the Ig-like V domain of PD-L1 were screened and identified from this combinatorial library using the yeast two hybrid system. The Z-j1 and Z-j2 recombinant affibody proteins were over produced in E.coli and purified. ELISA and GST pull-down assays showed that recombinant Z-j1 and Z-j2 affibody proteins bound with high affinity to PD-L1 and inhibited the interaction of PD-1/PD-L1. Thus, novel affibodies targeting the immune checkpoint PD-1/PD-L1 were identified and produced in this study and have the potential to be used in cancer immunotherapy.
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Antineoplásicos/química , Antígeno B7-H1/inmunología , Péptidos/genética , Receptor de Muerte Celular Programada 1/inmunología , Proteínas Recombinantes de Fusión/genética , Secuencia de Aminoácidos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Escherichia coli , Inmunoterapia , Biblioteca de Péptidos , Péptidos/química , Dominios Proteicos , Proteínas Recombinantes de Fusión/química , Proteína Estafilocócica A/química , Proteína Estafilocócica A/genéticaRESUMEN
Papillary thyroid carcinoma (PTC) is an aggressive histological subtype of thyroid carcinoma (THCA), whose occurrence rate is high. The participation of long noncoding RNAs in the pathologies of cancers has attracted significant attention during the past decades. The purpose of the current study is to investigate the role of NR2F1 antisense RNA 1 (NR2F1-AS1) in PTC. The expression of NR2F1 in THCA samples was analyzed by bioinformatics tool gene expression profiling interactive analysis. Levels of NR2F1-AS1, microRNA-423-5p (miR-423-5p), and SRY-box 12 (SOX12) were evaluated by a quantitative reverse transcription-polymerase chain reaction and Western blot. The impact of NR2F1-AS1 on PTC cell proliferation and invasion was assessed by Cell Counting Kit-8, EdU, and Transwell invasion assays. The interactions among NR2F1-AS1, miR-423-5p, and SOX12 were determined by RNA immunoprecipitation and luciferase reporter assays. Consequently, we found that NR2F1-AS1 and SOX12 levels were elevated in PTC, whereas miR-423-5p was downregulated in PTC cells. Functionally, NR2F1-AS1 silence led to reduced proliferation and invasion of PTC cells. Mechanistically, NR2F1-AS1 interacted with miR-423-5p to induce SOX12 expression in PTC cells. In conclusion, the present study firstly stated that NR2F1-AS1 regulated miR-423-5p/SOX12 to promote proliferation and invasion of PTC, indicating NR2F1-AS1 as a potential novel target for the molecular-targeted therapy of PTC.
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Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , ARN sin Sentido/genética , ARN Largo no Codificante/genética , Factores de Transcripción SOXC/metabolismo , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Factor de Transcripción COUP I/genética , Proliferación Celular , Humanos , Invasividad Neoplásica , Factores de Transcripción SOXC/genética , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Células Tumorales CultivadasRESUMEN
Operating chemical looping at moderate temperatures circumvents the issue that the sintering of oxygen carrier materials is serious at typical operating conditions, 800-950 °C. However, lower temperatures can lead to deterioration on the reaction kinetics and thereby the low H2 production rate and yield. Here, we present several doped spinel oxides consisting of earth-abundant elements for chemical looping water splitting. By virtue of the ability of the Cu dopant to improve the reduction of the Co-based binary spinel, the high reducibility of the dopants in the reduction period, as well as the phase reversibility in the water splitting period, Cu0.25Co0.25Fe2.5Oy shows a high hydrogen yield (â¼11.9 mmol g-1) and an average hydrogen production rate (â¼137.7 µmol g-1 min-1) at 550 °C, with negligible decays in repetitive redox cycles. The performance of this material is comparable to that of the state-of-the-art perovskites which usually contain rare-earth metals, enabling its potential in industrial implementation.
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A newly prepared tetraphenylethylene-based (TPE-based) covalent organic polymer (COP) named COP-1 exhibits high selectivity for sensing Fe3+ and the limit of detection (LOD) for Fe3+ is 0.42 µM, which is lower than the reported metal-free porous polymers. Furthermore, a WLED is fabricated and the CIE coordinates are (0.32, 0.33), very close to pure white light. The COP-1 shows potential applications in biosensors of Fe3+ and preparation of WLEDs.
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SCC-S2 overexpression has been implicated in several human cancers, its correlation with prognosis and the mechanism how it reserved biological roles are still uncertain. The current study demonstrated that, in 142 archived colorectal carcinoma (CRC) tissue samples, SCC-S2 expression was significantly correlated with higher histological grade ( p=0.001), tumor invasion ( p=0.001), advanced Dukes staging ( p=0.002), positive regional lymph node metastasis ( p=0.024), and poor overall survival ( p<0.001). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Transwell assays showed that SCC-S2 significantly promoted the proliferation and invasion. SCC-S2 expression was also accompanied by the overexpression CyclinD1, matrix metalloproteinase-7 (MMP-7), active-ß-catenin, yes-associated protein (YAP), and connective tissue growth factor (CTGF), as well as the depression of p-large tumor suppressor kinase 1 (p-LATS1) and p-YAP. Moreover, SCC-S2 interacted and colocalized with LATS1, the interaction may interrupt Hippo signaling and thereafter activate canonical Wnt signaling. In conclusion, our data suggested that SCC-S2 was associated with the progression and unfavorable prognosis of CRCs. Meanwhile, SCC-S2 facilitated canonical Wnt signaling and its downstream effectors (CyclinD1, MMP-7) and promoted tumor proliferation and invasion, which depended on the inhibition of Hippo signaling induced by SCC-S2-LATS1 interaction. These results indicated that SCC-S2 might be used as a novel target for the prevention and treatment of colorectal cancer.
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Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas/metabolismo , Vía de Señalización Wnt , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Reguladoras de la Apoptosis , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Vía de Señalización Hippo , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Fosforilación , Pronóstico , Proteínas/genéticaRESUMEN
To understand the genetic causes of pancreatic cancer (PC), we conducted a genome-wide association study (GWAS) using the diversity outbred (DO) mice population to identify susceptibility genes underlying 7,12-dimethylbenzanthraene (DMBA) induced PC. The phenotype studied was the percent PC lesion area in the DO mice population. We genotyped 7851 SNP markers specifically designed for DO mice across the whole mouse genome. Four susceptibility genes with P values exceeding the genome-wide threshold for percent PC lesion area (Pâ¯<â¯2.37â¯×â¯10-6) were identified, i.e., Epha4, Gpc5, Kcnj6, Arid1b. The most significant SNP of Gpc5 (UNC140360310) that is associated with PC lesion area in mice also significantly influences the Gpc5 expression, suggesting that this Gpc5 SNP exerts its role in PC through cis-regulating the gene expression of Gpc5. Together, our data supported that Gpc5 as a tumor suppressor gene involved in the etiology of PC.
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Genes Relacionados con las Neoplasias , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Polimorfismo de Nucleótido Simple , Animales , Femenino , Estudio de Asociación del Genoma Completo , Masculino , Ratones , Ratones Endogámicos , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologíaRESUMEN
BACKGROUND: Postoperative bile leak is a major surgical morbidity after curative resection with hepaticojejunostomy for hilar cholangiocarcinoma, especially in Bismuth-Corlette types III and IV. This retrospective study assessed the effectiveness and safety of an autologous hepatic round ligament flap (AHRLF) for reducing bile leak after hilar hepaticojejunostomy. METHODS: Nine type III and IV hilar cholangiocarcinoma patients were consecutively hospitalized for elective perihilar partial hepatectomy with hilar hepaticojejunostomy using an AHRLF between October 2009 and September 2013. The AHRLF was harvested to reinforce the perihilar hepaticojejunostomy. Main outcome measures included operative time, blood loss, postoperative recovery times, morbidity, bile leak, R0 resection rate, and overall survival. RESULTS: All patients underwent uneventful R0 resection with hilar hepaticojejunostomy. No patient experienced postoperative bile leak. CONCLUSIONS: The AHRLF was associated with lack of bile leak after curative perihilar hepatectomy with hepaticojejunostomy for hilar cholangiocarcinoma, without compromising oncologic safety, and is recommended in selected patients.
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Fuga Anastomótica/etiología , Fuga Anastomótica/cirugía , Neoplasias de los Conductos Biliares/complicaciones , Bilis , Tumor de Klatskin/complicaciones , Complicaciones Posoperatorias , Ligamento Redondo del Hígado , Colgajos Quirúrgicos , Anciano , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/cirugía , Femenino , Estudios de Seguimiento , Hepatectomía/métodos , Humanos , Tumor de Klatskin/diagnóstico , Tumor de Klatskin/cirugía , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Resultado del TratamientoRESUMEN
PANCREATIC tuberculosis (TB) is a rare disease and its diagnosis is difficult because of the lack of specific clinical manifestations. Computed tomography (CT) and magnetic resonance imaging (MRI) have some diagnostic values in this disease, but it is easy to misdiagnose pancreatic TB as a pancreatic tumor.1 In this article, we present a case of non-immunocompromised patient developing an isolated pancreatic TB, report the CT and MRI findings, and the surgical procedure for it.