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1.
BMC Pulm Med ; 24(1): 329, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982416

RESUMEN

BACKGROUND: The incidence of pneumothorax is higher in patients with emphysema who undergo percutaneous lung biopsy. Needle embolization has been shown to reduce the incidence of pneumothorax in patients with emphysema. Existing studies have reported small sample sizes of patients with emphysema, or the degree of emphysema has not been graded. Therefore, the efficacy of biopsy embolization in the prevention of pneumothorax induced by percutaneous pulmonary biopsy in patients with emphysema remains to be determined. METHODS: In this retrospective, controlled study, patients with emphysema who underwent CT-guided PTLB were divided into two groups: group A (n = 523), without tract embolization, and Group B (n = 504), with tract embolization. Clinical and imaging features were collected from electronic medical records and Picture Archiving and Communication Systems. Univariate and multivariate analyses were performed to identify risk factors for pneumothorax and chest tube placement. RESULTS: The two groups did not differ significantly in terms of demographic characteristics and complications other than pneumothorax. The incidence of pneumothorax and chest tube placement in group B was significantly lower than in group A (20.36% vs. 46.12%, p < 0.001; 3.95% vs. 9.18%, p < 0.001, respectively). In logistic regression analyses, variables affecting the incidence of pneumothorax and chest tube placement were the length of puncture of the lung parenchyma (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07-1.30, p = 0.001; OR = 1.55, 95% CI: 1.30-1.85, p < 0.001, respectively), tract embolization (OR = 0.31, 95% CI: 0.24-0.41, p < 0.001; OR = 0.39, 95% CI: 0.22-0.69, p = 0.001, respectively), and grade of emphysema. CONCLUSIONS: Tract embolization with gelatin sponge particles after CT-guided PTLB significantly reduced the incidence of pneumothorax and chest tube placement in patients with emphysema. Tract embolization, length of puncture of the lung parenchyma, and grade of emphysema were independent risk factors for pneumothorax and chest tube placement. TRIAL REGISTRATION: Retrospectively registered.


Asunto(s)
Embolización Terapéutica , Biopsia Guiada por Imagen , Pulmón , Neumotórax , Enfisema Pulmonar , Tomografía Computarizada por Rayos X , Humanos , Neumotórax/etiología , Neumotórax/prevención & control , Neumotórax/epidemiología , Femenino , Masculino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Embolización Terapéutica/métodos , Pulmón/patología , Pulmón/diagnóstico por imagen , Factores de Riesgo , Modelos Logísticos , Tubos Torácicos , Esponja de Gelatina Absorbible/administración & dosificación , Incidencia , Análisis Multivariante , Anciano de 80 o más Años , Radiografía Intervencional/métodos
2.
Br J Cancer ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890443

RESUMEN

BACKGROUND: The combined use of CDK4/6 inhibitors and mTOR inhibitors has achieved some clinical success in ccRCC. Exploring the underlying mechanism of the CDK4/6 pathway in cancer cells and the drug interactions of CDK4/6 inhibitors in combination therapy could help identify new therapeutic strategies for ccRCC. Notably, CDK4/6 inhibitors inactivate the mTOR pathway by increasing the protein levels of TSC1, but the mechanism by which CDK4/6 inhibitors regulate TSC1 is still unclear. METHODS: Mass spectrometry analysis, coimmunoprecipitation analysis, GST pull-down assays, immunofluorescence assays, Western blot analysis and RT‒qPCR analysis were applied to explore the relationships among CDK4, RNF26 and TSC1. Transwell assays, tube formation assays, CCK-8 assays, colony formation assays and xenograft assays were performed to examine the biological role of RNF26 in renal cancer cells.TCGA-KIRC dataset analysis and RT‒qPCR analysis were used to examine the pathways affected by RNF26 silencing. RESULTS: CDK4/6 inhibitors stabilized TSC1 in cancer cells. We showed that CDK4 enhances the interaction between TSC1 and RNF26 and that RNF26 activates the mTOR signaling pathway in ccRCC, contributes to ccRCC progression and angiogenesis, and promotes tumorigenesis. We then found that RNF26 functions as an E3 ligase of TSC1 to regulate CDK4-induced TSC1. This finding suggested that RNF26 promotes ccRCC progression and angiogenesis to some extent by negatively regulating TSC1. CONCLUSION: Our results revealed a novel CDK4/RNF26/TSC1 axis that regulates the anticancer efficacy of CDK4/6 inhibitors and mTOR inhibitors in ccRCC.

3.
CNS Neurosci Ther ; 30(6): e14762, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38924691

RESUMEN

AIM: To evaluate the association between frailty and postoperative delirium (POD) in elderly cardiac surgery patients. METHODS: A retrospective study was conducted of older patients admitted to the intensive care unit after cardiac surgery at a tertiary academic medical center in Boston from 2008 to 2019. Frailty was measured using the Modified Frailty Index (MFI), which categorized patients into frail (MFI ≥3) and non-frail (MFI = 0-2) groups. Delirium was identified using the confusion assessment method for the intensive care unit and nursing notes. Logistic regression models were used to examine the association between frailty and POD, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Of the 2080 patients included (median age approximately 74 years, 30.9% female), 614 were frail and 1466 were non-frail. The incidence of delirium was significantly higher in the frail group (29.2% vs. 16.4%, p < 0.05). After adjustment for age, sex, race, marital status, Acute Physiology Score III (APSIII), sequential organ failure assessment (SOFA), albumin, creatinine, hemoglobin, white blood cell count, type of surgery, alcohol use, smoking, cerebrovascular disease, use of benzodiazepines, and mechanical ventilation, multivariate logistic regression indicated a significantly increased risk of delirium in frail patients (adjusted OR: 1.61, 95% CI: 1.23-2.10, p < 0.001, E-value: 1.85). CONCLUSIONS: Frailty is an independent risk factor for POD in older patients after cardiac surgery. Further research should focus on frailty assessment and tailored interventions to improve outcomes.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Delirio , Fragilidad , Complicaciones Posoperatorias , Humanos , Femenino , Masculino , Anciano , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Delirio/epidemiología , Delirio/etiología , Delirio/diagnóstico , Fragilidad/diagnóstico , Fragilidad/epidemiología , Anciano de 80 o más Años , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Estudios Retrospectivos , Estudios de Cohortes , Factores de Riesgo
4.
Plant Physiol Biochem ; 206: 108302, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38171134

RESUMEN

Yellow seed is one desirable trait with great potential to improve seed oil quality and yield. The present study surveys the redundant role of BnTTG1 genes in the proanthocyanidins (PA) biosynthesis, oil content and abiotic stress resistance. Stable yellow seed mutants were generated after mutating BnTTG1 by CRISPR/Cas9 genome editing system. Yellow seed phenotype could be obtained only when both functional homologues of BnTTG1 were simultaneously knocked out. Homozygous mutants of BnTTG1 homologues showed decreased thickness and PA accumulation in seed coat. Transcriptome and qRT-PCR analysis indicated that BnTTG1 mutation inhibited the expression of genes involved in phenylpropanoid and flavonoid biosynthetic pathways. Increased seed oil content and alteration of fatty acid (FA) composition were observed in homozygous mutants of BnTTG1 with enriched expression of genes involved in FA biosynthesis pathway. In addition, target mutation of BnTTG1 accelerated seed germination rate under salt and cold stresses. Enhanced seed germination capacity in BnTTG1 mutants was correlated with the change of expression level of ABA responsive genes. Overall, this study elucidated the redundant role of BnTTG1 in regulating seed coat color and established an efficient approach for generating yellow-seeded oilseed rape genetic resources with increase oil content, modified FA composition and resistance to multiple abiotic stresses.


Asunto(s)
Brassica napus , Brassica rapa , Brassica napus/genética , Germinación/genética , Semillas/genética , Semillas/metabolismo , Brassica rapa/genética , Mutagénesis , Estrés Fisiológico/genética , Aceites de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
5.
World J Urol ; 41(3): 653-662, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35852595

RESUMEN

BACKGROUND: Artificial intelligence ultrasound of prostate (AIUSP)-targeted biopsy has been used for prostate cancer (PCa) diagnosis. The objective of this prospective multi-center head-to-head clinical randomized comparative trail (RCT) is to compare PCa detection rate in the TRUS-guided 12-core standard systematic biopsy (TRUS-SB) group and cognitive fused mpMRI-guided 12-core biopsy (mpMRI) group against AIUSP group. METHODS: Four hundred patients were randomized to three arms and underwent biopsies by TRUS-SB (n = 133), mpMRI (n = 134), and AIUSP (n = 133) between January 2015 and December 2017. In TRUS-SB group, a standard 12-core systematic biopsy was performed. In mpMRI group, mpMRI-suspicious lesions (PI-RADS 3-5) were targeted by 2-core biopsy followed by a 10-core systematic biopsy. Otherwise, 12-core systematic biopsy was performed. In AIUSP group, a 6-core targeted biopsy was performed. The primary endpoint was PCa detection rate. RESULTS: AIUSP detected the highest rate of PCa (66/133, 49.6%) compared to TRUS-SB (46/133, 34.6%, p = 0.036) and mpMRI (48/134, 35.8%, p = 0.052). Compared to TRUS-SB (35/133, 26.3%) and mpMRI (31/134, 23.1%) groups, clinically significant PCa (csPCa) detection rate was 32.3% (43/133) in AIUSP group. Overall biopsy core positive rate in the TRUS-SB group (11.0%, 176/1598) and in the mpMRI group (12.7%, 204/1608) was significantly lower than that in the AIUSP group (22.7%, 181/798, p < 0.001). CONCLUSIONS: AIUSP detected the highest rate of overall and significant PCa compared to TRUS-SB and mpMRI, and could be used as an alternative to systematic biopsy in the future. REGISTRATION: This trial was registered in ISRCTN (ISRCTN18033113).


Asunto(s)
Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Próstata/patología , Imagen por Resonancia Magnética , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Biopsia , Biopsia Guiada por Imagen
6.
Chemistry ; 29(4): e202202047, 2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36259356

RESUMEN

The solvothermal reactions of CoCl2 ⋅ 6H2 O, 3,5-pyridinedicarboxylic acid (H2 L) and isonicotinic acid (HL1 )/3-amino isonicotinic acid (HL2 )/3-chloro isonicotinic acid (HL3 ) successfully led to three tfz-d topological pillar-layer [Co4 (µ-F)2 (COO)6 (NC5 H4 )4 ] cluster-based MOFs, namely, [Co4 (µ-F)2 (L)2 (L1 )2 ⋅ 2DMA] ⋅ DMA ⋅ 2H2 O (SNNU-Bai76, SNNU-Bai=Shaanxi Normal University Bai's group), [Co4 (µ-F)2 (L)2 (L2 )2 ⋅ 2H2 O] ⋅ 2DMA ⋅ 2H2 O (SNNU-Bai77) and [Co4 (µ-F)2 (L)2 (L3 )2 ⋅ 2H2 O] ⋅ 2DMF ⋅ 2H2 O (SNNU-Bai78). With the 2D pore channels in SNNU-Bai76 and SNNU-Bai77 being tuned to the 1D pore channel in SNNU-Bai78, C3 H8 and C2 H6 adsorption uptakes are apparently improved and the IAST selectivities of C3 H8 /CH4 and C2 H6 /CH4 almost remain, which indicate that SNNU-Bai78 may be one potential separation material for the pipeline natural gas purification. These were further confirmed by the breakthrough experiments for the simulated pipeline natural gas (C3 H8 /C2 H6 /CH4 : 5/10/85 gas mixture) of three isostructural MOFs. Furthermore, GCMC simulations revealed that due to one of the pore channels blocked by Cl atoms in a couple of 3-chloro isonicotinic acid with the changed conformation as the pillar, the pore wall of the formed 1D pore channel in SNNU-Bai78 may interact with the adsorbed C3 H8 or C2 H6 molecule more strongly, for which more atoms of framework at the new adsorption site will interact with the adsorbed gas molecule by more intermolecular interactions. This was also evidenced by the increased binding energies, being consistent with the tuning of adsorption enthalpies for C3 H8 and C2 H6 gas molecules, and the reduced C3 H8 and C2 H6 gas diffusion coefficients in SNNU-Bai78. Very interestingly, this work is the first example of finely tuning the pore connectivity of MOFs toward strengthened host-guest interactions for the gas adsorption and separation.

7.
ACS Appl Mater Interfaces ; 13(34): 40713-40723, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34405673

RESUMEN

Due to the ultralow amounts of C3H8 and C2H6 gases, to design and synthesize water-stable MOFs that are promising for real-world efficient pipeline natural gas (NG) upgrading by the recovery of individual C3H8 and C2H6 gases is still a great challenge. Here, a N/O/F heteroatom-rich and rooflike [Cu(II)4Cu(I)2(COO)4(tetrazolyl)6] cluster-based ultra-microporous tsi-MOF (SNNU-Bai68) was afforded as a multiple heteroatom-rich and curved-surface-shaped cluster-based ultra-microporous MOF and the first porous MOF based upon such rooflike [Cu(II)xCu(I)y(tetrazolyl)z](2x+y-z)+ cluster. In SNNU-Bai68, the rooflike cluster was further assembled into a 1D chain secondary building block (SBB), which led to a high density of accessible potential adsorptive sites. Very interestingly, it exhibited the most promising balance of high gas adsorption uptakes at 0.01, 0.03, and 0.05 bar, high C3H8/CH4, C3H8/C2H6, and C2H6/CH4 adsorption selectivities, moderate adsorption enthalpies, and high water and chemical stability for pipeline natural gas upgrading by the recovery of individual C3H8 and C2H6 gases, which was further confirmed by the breakthrough experiments of the gas mixtures with/without 74% RH. Furthermore, the SC-XRD and GCMC studies revealed that the successful separation of C3H8, C2H6, and CH4 gases in SNNU-Bai68 is due to different synergistic effects of H-bonds between the frameworks at three adsorptive sites around each rooflike cluster and those different gas molecules, which were initially described systematically by the number of H atoms from the gas molecules, the total number of H-bonds within the synergistic H-bonds, and the binding energy of the framework at an adsorption site toward the gas molecules. In addition, this work may provide a method for the construction of a multiple heteroatom-rich and curved-surface-shaped cluster-based ultra-microporous MOF as a novel approach to build MOFs with polar pore surfaces, suitable pore sizes, and unique pore shapes to maximize the synergistic H-bonds between the framework and guests.

8.
Dig Liver Dis ; 53(11): 1499-1505, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33896751

RESUMEN

PURPOSE: To determine the safety and efficacy of microsphere embolization plus transarterial infusion chemotherapy for the treatment of gastroesophageal junction cancer with hepatic metastasis. METHODS: Sixty patients with gastroesophageal junction cancer and hepatic metastasis were randomly divided into two groups: group A (treatment group), which was treated with transarterial infusion chemotherapy plus microsphere embolization for gastroesophageal cancer, and with transarterial chemoembolization for hepatic metastasis; and group B (control group), which was treated with transarterial infusion chemotherapy for gastroesophageal cancer, and with transarterial chemoembolization for hepatic metastasis. The chemotherapy regimen used consisted of oxaliplatin plus FUDR. The embolization agent used for gastroesophageal cancer and the hepatic metastasis were Embosphere and ultra-liquefied lipiodol, respectively. RESULTS: The median survival time of patients in group A was 19 months, with survival rates at 12, 18, and 24 months of 93.3%, 60.0%, and 23.3%, respectively. The median survival time of patients in group B was 13 months, with survival rates at 12, 18, and 24 months of 60.0%, 30.0%, and 3.3%, respectively. There was a significant difference in survival between the two groups (P = 0.00). One month after treatment, the severity of dysphagia was significantly less in group A, as compared to that in group B (p < 0.001). CONCLUSION: Treatment of gastroesophageal junction cancer with hepatic metastasis by transarterial infusion chemotherapy plus microsphere embolization can rapidly reduce tumor size near the gastroesophageal junction. This treatment is an effective therapeutic option for these patients as it can relieve dysphagia and improve long-term survival rate.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma Hepatocelular/secundario , Quimioembolización Terapéutica/métodos , Neoplasias Esofágicas/patología , Neoplasias Hepáticas/secundario , Anciano , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Trastornos de Deglución , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad
9.
Front Oncol ; 11: 806907, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35004330

RESUMEN

BACKGROUND AND AIMS: This study investigated the feasibility, safety, and efficacy of transarterial chemoembolization (TACE) combined with CT-guided 125iodine seed implantation for treatment of hepatocellular carcinoma (HCC) with first-branch portal vein tumor thrombosis (PVTT). METHODS: This prospective, controlled, multicenter study included HCC patients with Barcelona Clinic Liver Cancer stage C disease and PVTT in the right and/or left portal veins. Patients were treated with either TACE and sorafenib or TACE and CT-guided 125iodine seed implantation and regularly evaluated for clinical response and adverse events, with treatment termination resulting from declining clinical status, loss to follow-up, or death. RESULTS: This study demonstrated a significant between-group difference in median overall survival (OS); therefore, it was terminated early. A total of 123 patients were included in this study, with 52 patients in the TACE-sorafenib group and 71 patients in the TACE-125iodine group, without significant differences in baseline characteristics between groups. The median OS was 8.3 months (95% CI: 6.105-10.495) in the TACE-sorafenib group and 13.8 months (95% CI: 9.519-18.081) in the TACE-125iodine group. In a subgroup analysis of type IIa versus type IIb PVTT, the median OS was 17.5 months for type IIa and 7.1 months for IIb in the TACE-125iodine group. The median OS was 9.3 months for IIa and 4.0 months for IIb in the TACE-sorafenib group. Univariate and multivariate analyses confirmed that the PVTT type and treatment strategy were significant independent factors affecting OS. The objective response rates (ORR) for intrahepatic lesions and PVTT showed significant differences between groups. Most patients in both groups experienced minor adverse events related to TACE. The overall incidence of sorafenib-related adverse events or toxic effects was 90.4% in TACE-sorafenib group. In the TACE-125iodine group, the incidence of pneumothorax and minor hepatic subcapsular hemorrhage were 7.04% and 9.86%, respectively. CONCLUSIONS: This study showed that TACE-125iodine treatment significantly enhanced survival of patients with HCC and type II PVTT, especially subtype IIa, with minimal adverse events. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trials Database, identifier ChiCTR-ONN-16007929.

10.
J Exp Med ; 217(2)2020 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-31658987

RESUMEN

Asthenozoospermia is a common cause of male infertility, but its etiology remains incompletely understood. We recruited three Pakistani infertile brothers, born to first-cousin parents, displaying idiopathic asthenozoospermia but no ciliary-related symptoms. Whole-exome sequencing identified a missense variant (c.G5408A, p.C1803Y) in DNAH17, a functionally uncharacterized gene, recessively cosegregating with asthenozoospermia in the family. DNAH17, specifically expressed in testes, was localized to sperm flagella, and the mutation did not alter its localization. However, spermatozoa of all three patients showed higher frequencies of microtubule doublet(s) 4-7 missing at principal piece and end piece than in controls. Mice carrying a homozygous mutation (Dnah17M/M) equivalent to that in patients recapitulated the defects in patients' sperm tails. Further examinations revealed that the doublets 4-7 were destabilized largely due to the storage of sperm in epididymis. Altogether, we first report that a homozygous DNAH17 missense variant specifically induces doublets 4-7 destabilization and consequently causes asthenozoospermia, providing a novel marker for genetic counseling and diagnosis of male infertility.


Asunto(s)
Astenozoospermia/genética , Dineínas Axonemales/genética , Mutación Missense , Cola del Espermatozoide/patología , Adulto , Animales , Astenozoospermia/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Genotipo , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Espermatozoides/patología , Testículo/patología , Transfección
11.
Biomolecules ; 9(11)2019 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-31726660

RESUMEN

Pod shattering resistance is an essential component to achieving a high yield, which is a substantial objective in polyploid rapeseed cultivation. Previous studies have suggested that the Arabidopsis JAGGED (JAG) gene is a key factor implicated in the regulatory web of dehiscence fruit. However, its role in controlling pod shattering resistance in oilseed rape is still unknown. In this study, multiplex genome editing was carried out by the CRISPR/Cas9 system on five homoeologs (BnJAG.A02, BnJAG.C02, BnJAG.C06, BnJAG.A07, and BnJAG.A08) of the JAG gene. Knockout mutagenesis of all homoeologs drastically affected the development of the lateral organs in organizing pod shape and size. The cylindrical body of the pod comprised a number of undifferentiated cells like a callus, without distinctive valves, replum, septum, and valve margins. Pseudoseeds were produced, which were divided into two halves with an incomplete layer of cells (probably septum) that separated the undifferentiated cells. These mutants were not capable of generating any productive seeds for further generations. However, one mutant line was identified in which only a BnJAG.A08-NUB-Like paralog of the JAG gene was mutated. Knockout mutagenesis in BnJAG.A08-NUB gene caused significant changes in the pod dehiscence zone. The replum region of the mutant was increased to a great extent, resulting in enlarged cell size, bumpy fruit, and reduced length compared with the wild type. A higher replum-valve joint area may have increased the resistance to pod shattering by ~2-fold in JAG mutants compared with wild type. Our results offer a basis for understanding variations in Brassica napus fruit by mutating JAG genes and providing a way forward for other Brassicaceae species.


Asunto(s)
Proteínas de Arabidopsis/genética , Brassica napus/genética , Proteínas de Ciclo Celular/genética , Frutas/genética , Edición Génica/métodos , Arabidopsis/genética , Brassica napus/crecimiento & desarrollo , Sistemas CRISPR-Cas/genética , Frutas/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Genoma de Planta/genética , Mutación/genética
12.
Oncol Lett ; 18(3): 2340-2347, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31452730

RESUMEN

Voltage-dependent anion channels (VDACs) are situated in the outer membrane of the mitochondria and serve as gatekeepers that control metabolite and ion exchange between the cytosol and mitochondria. VDAC1 is one of the most studied members of the VDAC protein family and is overexpressed in multiple types of cancer. However, the specific biological function and regulatory mechanism of VDAC1 in breast cancer remains unclear. The present study investigated the biological role of VDAC1 in breast cancer cells using an MTS assay. The association of clinicopathological features with VDAC1 in breast cancer was analyzed by Gene Expression Profiling Interactive Analysis. The regulatory mechanism of VDAC1 was determined by cell transfection, western blot analysis, reverse transcription-quantitative (q)PCR analysis, chromatin immunoprecipitation (ChIP) and ChIP-qPCR analysis. The results of the present study demonstrated that VDAC1 promoted breast cancer proliferation and was associated with a poor prognosis in patients with breast cancer. Additionally, it was observed that the expression of VDAC1 could be decreased by the bromodomain inhibitor (JQ1), and bromodomain-containing protein 4 (BRD4) was indicated to be a regulator of VDAC1. Furthermore, results suggested that VDAC1 may be involved in the resistance of breast cancer to JQ1. Collectively, the present findings uncovered important aspects of the function of VDAC1 in the tumor progression of breast cancer, and may provide a basis for potential therapeutic strategies for the treatment of breast cancer.

13.
Oncol Lett ; 16(6): 7008-7019, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30546434

RESUMEN

Brain metastasis occurs in ~30% of patients with breast cancer, and patients with human epidermal growth factor receptor 2 (HER2)+ breast cancer have a particularly high frequency of brain metastasis. Weighted gene co-expression network analysis was conducted to identify the hub differentially expressed genes from patients with HER2+ breast cancer between brain metastases and primary tumors. The potential candidate genes were investigated in another set of patient samples to confirm their relevance. The results indicated that a number of pathways altered significantly when breast cancer metastasized to the brain. Cyclophilin A (CypA) and ribosomal protein L17 (RPL17) were overexpressed in breast cancer-associated brain metastases, whereas tumor protein 63 (TP63) and von Willebrand factor A domain-containing 8 (VWA8) were significantly downregulated in breast cancer brain metastases. Furthermore, the expression of CypA and RPL17 in brain metastases were significantly increased compared with that in primary breast tumors, and the expression of TP63 and VWA8 in brain metastases were significantly decreased. This result indicated that the significant differences in expression observed between primary breast tumors and brain metastases were derived from significantly altered systems, including gene modules rather than single genes.

14.
Medicine (Baltimore) ; 97(45): e13053, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30407303

RESUMEN

Systemic illustrations of spindle cell thyroid cancer (SCTC), based on a large cohort, are few. We investigated the prognosis of SCTC compared to the most common subtypes, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC).Information of patients with a diagnosis of SCTC, PTC, or FTC, between 2004 and 2013, was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Patient survival curves were investigated using Kaplan-Meier analyses, log-rank tests, and Cox proportional hazards regression analyses.In a Kaplan-Meier analysis of the entire cohort of thyroid cancer patients, cancer specific survival declined sharply for patients with SCTC, but declined more modestly for patients with PTC and FTC. Unadjusted Cox regression analysis and Kaplan-Meier curve analysis showed that SCTC had a poorer cancer-specific mortality and all-cause mortality compared to PTC and FTC. Similar results were obtained after adjustment for different confounding factors.Our study assessed the prognosis of SCTC, based on a large cohort, compared to PTC and FTC, and found relatively accurate hazard ratios of death rate in SCTC as compared to PTC and FTC. Thus, our findings would provide beneficial insights on patients with SCTC, and aid in treatment decision making, more radical treatment like total-thyoridectomy and/or plus central lymph node dissection should be performed for patients with SCTC.


Asunto(s)
Adenocarcinoma Folicular/mortalidad , Carcinoma Papilar/mortalidad , Carcinoma/mortalidad , Neoplasias de la Tiroides/mortalidad , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Regresión , Programa de VERF , Cáncer Papilar Tiroideo
15.
Oncotarget ; 8(57): 97613-97622, 2017 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-29228637

RESUMEN

OBJECTIVE: Though synergy of sorafenib and transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) is well discussed in previous reports, association of lipiodol retention by sorafenib addition to TACE with the survival outcomes remain elusive. Therefore, we studied the impact of sorafenib addition to TACE on survival outcomes mediated by lipiodol retention. MATERIALS AND METHODS: This is a long-term, retrospective, single-center study using medical records of patients diagnosed with HCC at the Department of Interventional Radiology of Zhengzhou University Affiliated Cancer Hospital (China) between April 2004 and March 2012. RESULTS: Lipiodol deposition of > 50% was significantly increased in TACE + sorafenib group (70.87%) compared to TACE alone group (45.11%) (P = 0.0001). Significant increase in lipiodol deposition with sorafenib treatment was observed compared to TACE alone group (OR = 0.449, P = 0.041). The median overall survival in TACE + sorafenib and TACE alone groups were 38 months [95% CI = 9.772-56.228] and 31 months [95% CI = 21.855-40.145] respectively. Also, the hazard of death was comparatively greater in TACE alone group than TACE + sorafenib group [HR = 1.071]. Response rate to the therapy significantly increased after sorafenib administration to TACE patients, [compared to TACE alone treatment [69/103 (66.99%)] vs 55/133 (41.35%)], P = 0.0001. CONCLUSIONS: Lipiodol deposition is significantly increased upon sorafenib addition after TACE. However, there was no significant impact of lipiodol deposition on the survival benefits exerted by the synergistic combination and hence, future prospective trails are warranted to validate the findings of this study.

16.
Int J Surg ; 40: 187-197, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28302449

RESUMEN

BACKGROUND: laparoscopic appendectomy(LA) has proved to be a safe alternative to open appendectomy(OA) in uncomplicated appendicitis; however, the feasibility of LA for complicated appendicitis(CA) has not been conclusively determined. OBJECTIVES: To assess the feasibility and safety of LA for CA through a systematic review and meta-analysis. METHODS: A literature search in PubMed, Embase, Cochrane Library, and web of Science was performed for eligible studies published from the inception of the databases to January 2016. All studies comparing LA and OA for CA were reviewed. After literature selection, data extraction and quality assessment were performed by two reviewers independently, and meta-analysis was conducted using Revman software, vision 5.2. RESULTS: Two randomized controlled trials (RCTs) and 14 retrospective cohort studies(RCSs) were finally identified. Our meta-analysis showed that LA for CA could reduce the rate of surgical site infections (SSIs) (OR = 0.28; 95% CI: 0.25 to0.31, P < 0.00001), but LA did not increase the rate of postoperative intra-abdominal abscess(IAA) (OR = 0.79; 95% CI: 0.45 to 1.34, P = 0.40). The results showed that the operating time in the LA groups was much longer than that in the OA groups (WMD = 13.78, 95% CI: 8.99 to 18.57, P < 0.00001). However, the length of hospital stays in the LA groups were significantly shorter than those in the OA groups (WMD = -2.47, 95%CI: -3.75 to -1.19, P < 0.0002), and the time until oral intake(TTOI) was much earlier in the LA groups than in the OA groups (WMD = -0.88, 95% CI: -1.20 to -0.55, P < 0.00001). No significant difference was observed in the times of postoperative analgesia between the two groups(P > 0.05). CONCLUSION: LA was feasible and safe for complicated appendicitis, and it not only could shorten the hospital stays and the time until oral intake, but it could also reduce the risk of surgical site infection.


Asunto(s)
Apendicectomía/métodos , Apendicitis/cirugía , Laparoscopía/métodos , Adulto , Apendicectomía/efectos adversos , Bases de Datos Factuales , Femenino , Humanos , Laparoscopía/efectos adversos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento
17.
PLoS One ; 11(10): e0163173, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27701426

RESUMEN

The processes governing tumor growth and angiogenesis are codependent. To study the relationship between them, we proposed a coupled hybrid continuum-discrete model. In this model, tumor cells, their microenvironment (extracellular matrixes, matrix-degrading enzymes, and tumor angiogenic factors), and their network of blood vessels, described by a series of discrete points, were considered. The results of numerical simulation reveal the process of tumor growth and the change in microenvironment from avascular to vascular stage, indicating that the network of blood vessels develops gradually as the tumor grows. Our findings also reveal that a tumor is divided into three regions: necrotic, semi-necrotic, and well-vascularized. The results agree well with the previous relevant studies and physiological facts, and this model represents a platform for further investigations of tumor therapy.


Asunto(s)
Modelos Biológicos , Neoplasias/patología , Neovascularización Patológica , Algoritmos , Inductores de la Angiogénesis , Simulación por Computador , Matriz Extracelular , Humanos , Neoplasias/metabolismo , Neovascularización Patológica/metabolismo , Microambiente Tumoral
19.
Asian Pac J Trop Med ; 9(2): 193-6, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26919955

RESUMEN

OBJECTIVE: To investigate the influence of lactulose on immunity of hepatocellular carcinoma (HCC) patients with hepatocirrhosis and hypersplenism after double-interventional therapies. METHODS: A total of 40 HCC patients with hepatocirrhosis and hypersplenism, hospitalized during January 2013 to June 2014, were enrolled and randomized into control group and observation group. Both groups received partial splenic embolization combined with transcatheter arterial chemoembolization. Besides, observation group orally took lactulose 30 mL/d. Four days before interventional therapies and at days 1, 3, 7 and 14 after therapies, fasting venous blood was collected to detect white blood cell count, red blood cell count (RBC), and platelet count (PLT). Four days before therapies and at days 7 and 14 after therapies, the levels of alanine aminotransferase, aspartate transaminase, total bilirubin, malondialdehyde, super-oxide dismutase (SOD), IFN-γ, and IL-4 as well as the distribution of T cell subsets in peripheral blood were tested. Complications were observed after interventional therapies. RESULTS: Before interventional therapies the levels of white blood cell count, PLT and RBC in both groups showed no difference, while after interventional therapies the levels of PLT and RBC in both groups showed an increasing tendency (P < 0.05). At day 14 after interventional therapies, the level of blood cell as well as that of SOD, IFN-γ and IL-4 in serum were significantly higher than that before therapies; meanwhile, the levels of alanine aminotransferase and total bilirubin of observation group after therapies were significantly lower than before and control group (P < 0.05), the levels of CD4(+)/CD8(+), SOD and IFN-γ were all higher than before and control group (P < 0.05). CONCLUSIONS: Oral administration of lactulose could adjust the imbalance of oxidation system/antioxidant system in HCC patients with hepatocirrhosis and hypersplenism after interventional therapies, and improve the antitumor immunity and prognosis.

20.
Oncotarget ; 7(6): 7241-52, 2016 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-26769845

RESUMEN

This study evaluated the factors impacting overall survival (OS) and time to progression (TTP) in patients with unresectable hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE). HCC patients were grouped based on tumor vascularity and lipidiol deposition after TACE. Tumor vascularity was classified based on contrast enhancement on arterial phase baseline CT scans. Lipiodol deposition was evaluated using CT scans. The progression-free rate was significantly higher in patients with good blood supply + good lipiodol deposition compared to those with good blood supply + poor lipiodol deposition. In patients with poor lipidiol deposition, risk of death was significantly positively correlated with stage, and negatively correlated with number of TACE procedures and degree of lipidiol deposition after the first TACE. Risk of disease progression in these patients was positively correlated with tumor size, and negatively correlated with number of TACE procedures and degree of lipidiol deposition after the first TACE. Our data showed that tumor vascularity and lipiodol deposition can be used as early radiological markers to identify patients who do not respond to TACE, and who can be considered earlier for alternative combination treatment strategies. Our data also indicated that poor lipiodol retention may predict a poor TTP and OS despite the blood supply status.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica , Aceite Etiodizado/uso terapéutico , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/tratamiento farmacológico , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Arteria Hepática , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Carga Tumoral
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