Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.215
Filtrar
1.
Nanotechnology ; 31(3): 035702, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31557749

RESUMO

The ability of light to carry and deliver orbital angular momentum (OAM) in the form of optical vortices has attracted much interest. Conventional optical vortices are usually generated by bulky or expensive devices, which would sharply decrease the integration of optical communication systems. Here we demonstrate efficient large-area wavelength-thick metasurfaces that have the ability to produce high-quality optical vortexes with arbitrary OAM and to focus the beams into wavelength-scale rings with efficiency as high as 80%. Moreover, we reveal the relationship between size and energy distribution of focal rings (FR) with different OAMs: as the number of OAM increases, the size of the FR is linearly increasing, the peak focusing intensity (FFI) is decreasing in inverse proportional type, while the total energy on the FR remain almost unchanged. Rigorous quantitative analysis about the coupling effect among nanoantennas and the chromatic aberrations of the proposed metasurfaces are further discussed. We envision such highly efficient metasurfaces for spiral focusing will have potential applications in optical tweezers and communications.

2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 636-645, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31699194

RESUMO

Objective To compare the differences in fecal flora among patients with esophageal cancer,gastric cancer,or colorectal cancer and between patients with gastrointestinal tumors and healthy people.Methods The 16S rRNA method was used to analyze the differences in fecal flora among 13 patients with esophageal squamous cell carcinoma,23 patients with gastric cancer,6 patients with colorectal cancer,and 49 healthy persons.Results Bifidobacterium,Faecalibacterium prausnitzii,and Ruminococcus callidus were less abundant in the fecal flora of cancer patients than in those of healthy controls(all P<0.05).Some species of Firmicutes and Actinobacteria were significantly reduced in the feces of patients with esophageal cancer or gastric cancer than in healthy people(P<0.05),whereas others showed consistency with the intestinal cancer group.Anti-tumor treatment,antibiotics,and lactic acid could affect the fecal flora of cancer patients.Conclusion The gut microbiota compositions(mainly Firmicutes and Actinobacteria)and some specific bacteria species in the feces of patients with esophageal cancer and gastric cancer are similar to those in the feces of patients with intestinal cancer,suggesting these bacteria may be involved in the development of upper gastrointestinal tumors.

4.
Int J Gynecol Pathol ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31569185

RESUMO

Endometrial stromal sarcoma (ESS) is a rare malignant tumor of the uterus that has been described as the second most common malignant uterine mesenchymal tumor. The Primary extrauterine ESS (EESS) is an extremely uncommon occurrence. We hereby report a new bona fide case of low-grade EESS in a 74-yr-old woman arising in the vagina, presenting as a polypoid mass associated with irregular vaginal bleeding. On examination, a 6×2×2 cm polypoid mass was found in the left vaginal wall. Consequently, the patient underwent partial vaginectomy and repair. No ESS or endometriotic lesion was found in the endometrium and bilateral adnexa. The diagnosis of ESS performed by typical pathologic and immunohistochemical evaluation was as follows: beta-catenin (+++), estrogen receptor (+++), progesterone receptor (++), vimentin (++), and uniformly negative for CD10, EMA, CD31, CD34, CD117,CD99, SMA, desmin, h-caldesmon, S-100, MelanA, and HMB45. She has remained disease free with no signs or symptoms of recurrent or advanced disease for 46 mo. Although CD10 is the most useful immunohistochemical marker for the diagnosis of this tumor, negative CD10 staining can be encountered with underfixation. Therefore, it is important to use a panel of immunostains that includes CD10, beta-catenin, and smooth muscle markers. The present study describes the clinical and pathologic features of low-grade EESS through a case report and literature review. To the best of our knowledge, this is the eighth report of EESS arising from the vagina.

5.
Biomed Chromatogr ; : e4701, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596954

RESUMO

Patrinia villosa (Thunb.) Juss. (PVJ) is described as pungent, bitter and slightly cold in Chinese medicine, and is associated with the large intestine, stomach and liver meridians. The preliminary experiments of our research team proved that PVJ total flavonoids have excellent inhibitory effects on liver cancer cells. And, the present experiment use the UPLC-Q-TOF-MS technology and serum pharmacochemistry methods to analyze the chemical components in vitro and in vivo of PVJ anti-liver tumors. The results show that a total of 14 chemical components are identified in the total flavonoids extract of PVJ, and it is mainly composed of flavonoids, flavonones, flavonols and phenolic acids. At the same time, 7 prototypical components and 7 metabolic components are detected in the drug-containing plasma. Hydrocaffeate and scutellarein are the phase I metabolites of caffeic acid and scutellarin, respectively. Sulfated apigenin, sulfated luteolin, sulfated kaempferol, and methylated kaempferol are the II phase metabolites of apigenin, luteolin, kaempferol, respectively. The experiment provides a reference for the research and development of anti-tumor drug candidates, and provides a basis for revealing the bioactive components of PVJ and anti-tumor mechanism.

6.
J Biol Chem ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594861

RESUMO

Constitutive activation of signal transducer and activator of transcription 3 (STAT3) occurs in approximately 70% of human cancers, and STAT3 is regarded as one of the most promising targets for cancer therapy. However, specific direct STAT3 inhibitors remain to be developed. Oridonin is an ent-kaurane plant-derived diterpenoid with anti-cancer and anti-inflammatory activities. Here, using an array of cell-based and biochemical approaches, including cell proliferation and apoptosis assays, pull-down and reporter gene assays, site-directed mutagenesis, and molecular dynamics analyses, we report that a thiazole-derived oridonin analog, CYD0618, potently and directly inhibits STAT3. We found that CYD0618 covalently binds to Cys-542 in STAT3 and suppresses its activity through an allosteric effect, effectively reducing STAT3 dimerization and nuclear translocation, as well as decreasing expression of STAT3-targeted oncogenes. Remarkably, CYD0618 not only strongly inhibited growth of multiple cancer cell lines that harbor constitutive STAT3activation, but it also suppressed in vivo tumor growth, via STAT3 inhibition. Taken together, our findings suggest Cys-542 as a druggable site for selectively inhibiting STAT3 and indicate that CYD0618 represents a promising lead compound for developing therapeutic agents against STAT3-driven diseases.

7.
In Vivo ; 33(6): 1865-1877, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662514

RESUMO

BACKGROUND/AIM: Muscle-invasive bladder cancer (MIBC) has long been recognized as a difficult to treat cancer type, thus a new treatment strategy is needed. The major purpose of the present study was to verify the anticancer effect of hyperforin and the mechanism through which it affects tumor cell growth and invasion in bladder cancer in vitro. MATERIALS AND METHODS: Bladder cancer TSGH-8301 cells were treated with different concentrations of hyperforin for different durations of time. The changes in cell viability, production of calcium and reactive oxygen species (ROS), and anti-apoptotic signaling were evaluated using MTT assay, flow cytometry, and western blot analysis. The effect of hyperforin on the expression of nuclear factor-kappaB (NF-ĸB) p65 (Ser276), tumor progression-associated proteins, as well as on cell invasion was investigated using western blotting and cell invasion assay, respectively. RESULTS: Hyperforin significantly induces apoptosis, extrinsic/intrinsic apoptotic signaling, accumulation of cytosol ROS, and calcium signalling. Hyperforin also significantly diminishes the expression of NF-ĸB p65 (Ser276), anti-apoptotic and tumor progression-associated proteins, as well as the cell invasion ability of TSGH-8301 cells. CONCLUSION: Our findings demonstrate that hyperforin triggers apoptosis depending on extrinsic/intrinsic pathways and suppresses NF-ĸB-mediated cell survival as well as the invasive properties of bladder cancer in vitro.

9.
World J Surg ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31637507

RESUMO

BACKGROUND: The prognostic significance of preoperative plasma fibrinogen in patients with operable gastric cancer remains under debate. This study aimed to elucidate the prognostic value of fibrinogen in gastric cancer patients underwent gastrectomy. METHODS: A total of 4351 patients with gastric cancer collected from three comprehensive medical centers were retrospectively evaluated. Patients were categorized by minimum P value using X-tile, while the baseline confounders for fibrinogen was balanced through propensity score matching (PSM). The relationships between fibrinogen and other clinicopathologic features were evaluated, and nomogram was constructed to assess its prognostic improvement compared with TNM staging system. RESULTS: Fibrinogen was significantly correlated with macroscopic type, tumor differentiation, tumor size, and T and N stage. The factors, fibrinogen and T stage as well as N stage, were identified to be independent prognostic factors after PSM. Nomogram based on fibrinogen demonstrated a smaller Akaike information criterion (AIC) and a larger concordance index (C-index) than TNM staging system, illustrating that fibrinogen might be able to improve the prognostic accuracy. CONCLUSIONS: Preoperative plasma fibrinogen levels in gastric cancer patients were significantly correlated with tumor progression, which could be regarded as a reliable marker for survival prognostic prediction.

10.
J Cell Physiol ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31637715

RESUMO

Lung adenocarcinoma (LUAD) is one of the most malignant tumor types worldwide. Our objective was to identify a genetic signature that could predict the prognosis of patients with LUAD. We extracted gene data sets from The Cancer Genome Atlas and obtained differentially expressed genes that were highly expressed at every stage. These genes were analyzed using gene set enrichment analysis to obtain four biological processes associated with LUAD. Subsequently, Cox univariate and multivariate analyses were performed to generate four optimized models (G2M checkpoint, E2F targets, mitotic spindle, and glycolysis). We identified a mitotic spindle-related signature (KIF15, BUB1, CCNB2, CDK1, KIF4A, DLGAP5, ECT2, and ANLN), which could be an independent prognostic indicator, to predict the prognosis of patients with LUAD. This new discovery should offer opportunities to explore the pathogenesis of LUAD and prove clinically useful in predicting LUAD patient prognosis.

11.
Electrophoresis ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31621929

RESUMO

Exosomes are vesicles with sizes ranging from 30 to 150 nm. The analysis and detection of blood exosomes offers an effective route for cancer diagnosis, prognosis assessment, and therapeutic evaluation of diseases. Due to the difference in separation procedure, collection method and the usage of anticoagulants, serum and plasma samples show diversity test results. In order to evaluate the isolation effect of exosomes in serum and plasma samples, two commonly used exosomal isolation methods, ultracentrifugation and polymer-based precipitation kit, were used, respectively. And the isolation effects were evaluated by comparing the composition and abundant of proteins from isolated exosomes based on MS-based proteomics analysis. The results showed that the plasma exosomes extracted by ultracentrifugation identified more exosome biomarkers, and the concentration of these biomarkers were higher than others. And plasma exosomes could be a better sample for blood-based proteomics research of exosomes. It would be more useful for future targeted biomarker discovery. This article is protected by copyright. All rights reserved.

12.
J Cell Biochem ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31633246

RESUMO

Gastric cancer (GC) is one of the most fatal common cancers in worldwide. Helicobacter pylori (H. pylori) infection is closely related to the development of GC, although the mechanism is still unclear. In our study, we aim to develop a robust messenger RNA (mRNA) signature associated with H. pylori (-) GC that can sensitively and efficiently predict the prognostic. The RNA-seq expression profile and corresponding clinical data of 598 gastric cancer samples and 63 normal samples obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database. Using gene set enrichment analysis H. pylori (+) GC and H. pylori (-) GC patients and normal samples to select certain genes for further analysis. Using univariate and multivariate Cox regression model to establish a gene signature for predicting the overall survival (OS). Finally, we identified G2/M related seven-mRNA signature (TGFB1, EGF, MKI67, ILF3, INCENP, TNPO2, and CHAF1A) closely related to the prognosis of patients with H. pylori (-) GC. The seven-mRNA signature was identified to act as an independent prognostic biomarker by stratified analysis and multivariate Cox regression analysis. It was also validated on two test groups from TCGA and GSE15460 and shown that patients with high-risk scores based on the expression of the seven mRNAs had significantly shorter survival times compared to patients with low-risk scores (P < .0001). In this study, we developed a seven-mRNA signature related to G2/M checkpoint from H. pylori (-) GCs that as an independent biomarker potentially with a good performance in predicting OS and might be valuable for the clinical management for patients with GC.

13.
Cancer Lett ; 469: 54-67, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31629932

RESUMO

Epithelial ovarian cancer (EOC) is responsible for nearly 140,000 deaths worldwide each year. MicroRNAs play critical roles in cancer development and progression. The function of microRNA miR-337-3p has been described in various cancers. However, the biological role of miR-337-3p and its molecular mechanisms underlying EOC initiation and progression have not been reported. Here, we reported that the expression of miR-337-3p is down-regulated in EOC tissues and low expression of miR-337-3p is correlated with advanced pathological grade for patients. Ectopic expression of miR-337-3p inhibited proliferation and induced apoptosis and cell cycle arrest in G0/G1 phase of EOC cells. PIK3CA and PIK3CB were revealed to be direct targets of miR-337-3p for reducing the activation of PI3K/AKT signaling pathway. PIK3CA and PIK3CB were discovered to affect cell proliferation of EOC cells in combination, and only when overexpressed simultaneously in miR-337-3p-expressing cells, could fully restore cell proliferation. In vivo investigation confirmed that miR-337-3p is a tumor suppressor that control expression of PIK3CA and PIK3CB encoded protein: p110α and p110ß. Altogether, our results demonstrate that miR-337-3p is a tumor suppressor in EOC that inhibits the expression of PIK3CA and PIK3CB.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31665807

RESUMO

Deregulation of microRNAs (miRNAs) leads to malignant growth and aggressive invasion during cancer occurrence and progression. miR-147b has emerged as one of the cancer-related miRNAs that are dysregulated in multiple cancers. Yet, the relevance of miR-147b in non-small-cell lung cancer (NSCLC) remains unclear. In the present study, we aimed to report the biological function and signaling pathways mediated by miR-147b in NSCLC. Our results demonstrate that miR-147b expression is significantly downregulated in NSCLC tissues and cell lines. Overexpression of miR-147b decreased the proliferative ability, colony-forming capability, and invasive potential of NSCLC cells. Notably, our study identified ribosomal protein S15A (RPS15A), an oncogene in NSCLC, as a target gene of miR-147b. Our results showed that miR-147b negatively modulates RPS15A expression in NSCLC cells. An inverse correlation between miR-147b and RPS15A was evidenced in NSCLC specimens. Moreover, miR-147b overexpression downregulated the activation of Wnt/ß-catenin signaling via targeting of RPS15A. Overexpression of RPS15A partially reversed the miR-147b-mediated antitumor effect in NSCLC cells. Collectively, these findings reveal that miR-147b restricts the proliferation and invasion of NSCLC cells by inhibiting RPS15A-induced Wnt/ß-catenin signaling and suggest that the miR-147b/RPS15A/Wnt/ß-catenin axis is an important regulatory mechanism for malignant progression of NSCLC.

15.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3763-3772, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602951

RESUMO

The detection of drug-induced anaphylactoid reactions remains a global challenge,still lacking mature and reliable animal models or test methods. Therefore,the purpose of this paper is to explore and establish the test methods and evaluation standards for anaphylactoid reactions that apply to injection drugs. Based on the anaphylactoid reaction symptoms of mice induced by intravenous injection drugs C48/40 and Tween 80,a list of systemic anaphylactoid reaction symptoms in mice was sorted out and an evaluation standard of anaphylactoid reactions symptoms was established by applying symptom intensity coefficient K( that can represent these verity of anaphylactoid reaction symptoms) and its calculation formula Accordingly,histamine,tryptase,and Ig E were selected as blood indicators of anaphylactoid reactions,so that a test method combining symptoms evaluation and blood makers detection was established.This test method could be used to evaluate the characteristics of anaphylactoid reactions: coefficient K,blood histamine levels were highly and positively correlated with C48/80 and Tween 80 dose; The log value of histamine was highly and positively correlated with K; tryptase level may rise,or remain steady,or drop,possibly associated with the characteristics of the tested object and time for blood taking; and Ig E level would drop or remain steady,but it would not rise,which can be clearly distinguished from type I allergic reactions. On this basis,tiohexol,iopromide,paclitaxel,Xuesaitong Injection,Shuanghuanglian Injection and Shengmai Injection were used to investigate the applicability. The testing results showed a high degree of consistency with the actual clinical situation. The results suggest that the method of systemic anaphylaxis test in mice has high sensitivity,specificity and good consistency with clinical practice.It is suggested to be further validated and popularized.


Assuntos
Anafilaxia/induzido quimicamente , Anafilaxia/diagnóstico , Modelos Animais de Doenças , Animais , Medicamentos de Ervas Chinesas/toxicidade , Histamina/sangue , Imunoglobulina E/sangue , Injeções Intravenosas , Camundongos , Choque/induzido quimicamente , Choque/diagnóstico , Testes de Toxicidade , Triptases/sangue
16.
Opt Express ; 27(14): 20073-20083, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31503757

RESUMO

Epsilon-and-mu-near-zero (EMNZ) medium which possessing close to zero permittivity and permeability has peculiar electromagnetic properties and can be utilized to design various electromagnetic functional devices. Recent theoretical research shows that EMNZ medium can be achieved by simply doping normal dielectric in an epsilon-near-zero (ENZ) medium, which is easier to obtain than EMNZ medium. Practically, the permittivity will cross zero in the terahertz regime for polar dielectrics and some semiconductors, and in the visible and ultraviolet for the noble metals. While in the microwave band, it is recently found that some magnetic materials can be used to realize the ENZ medium. Here in this paper, we extend the doping theory and propose the similar way for realizing EMNZ property in magnetic ENZ medium by adding dielectric dopant. Both the theoretical analysis and full wave simulation show EMNZ can be achieved by adjusting the parameters of normal dielectric dopants, such as the size, relative permittivity, as well as the number of dopants in a magnetic ENZ with arbitrary value of permeability. To verify the proposed theory, a practical electromagnetic tunneling structure is designed and tested based on an existing magnetic ENZ material through proper dielectric doping. The proposed design method may provide realistic and meaningful guidance for the realization and application of practical EMNZ medium at microwave frequency.

17.
Sensors (Basel) ; 19(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31510003

RESUMO

Navigation is a precondition for ocean space vehicles to work safely in polar regions. The traditional polar algorithms employ the grid strapdown inertial navigation system (SINS) as the backbone and Doppler velocity log (DVL) output velocity as measurements to constitute the integrated navigation system, of which, however, the position errors still accumulate with time. The ultra-short baseline (USBL) position system can provide position information that can be used to improve the performance of the SINS/DVL integrated system. Therefore, a grid SINS/DVL/USBL integrated algorithm for polar navigation is proposed in this paper. In order to extend the availability of the USBL and improve integration accuracy in polar regions, the USBL observation model is established based on the relative position measurement firstly. Then, a grid SINS/DVL/USBL integrated algorithm is proposed to fuse the information of these sensors with a modified Kalman filter (MKF) dealing with the sparse USBL output. Finally, a vector fault detection method, which takes the measurements as detection objects instead of the filter, is designed to locate the measurement fault and can be employed by the centralized filter to improve the fault-tolerant. Simulation and experiment results show that the proposed grid SINS/DVL/USBL integrated navigation system can further restrain SINS errors especially the position errors effectively. Meanwhile, the vector fault detection method can detect and isolate the fault measurements of centralized filter immediately and accurately. Therefore, the proposed fault-tolerant grid SINS/DVL/USBL integrated navigation algorithm can improve the reliability and accuracy of polar navigation for ocean space application.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31512996

RESUMO

BACKGROUND: Forkhead box C1 (FOXC1) is an important cancer associated gene in tumor. PPAR-γ and C/EBPα are both transcriptional regulators involved in tumor development. OBJECTIVE: We aimed to clarify the function of PPAR-γ, C/EBPα in hepatocellular carcinoma (HCC) and relationship of PPAR-γ, C/EBPα and FOXC1 in HCC. METHOD: Western blotting, immunofluorescent staining and immunohistochemistry were used to evaluate protein expression. qRT-PCR was used to assess mRNA expression. Co-IP was performed to detect the protein interaction. And ChIP and fluorescent reporter detection were used to determine the binding between protein and FOXC1 promoter. RESULTS: C/EBPα could bind to FOXC1 promoter and PPAR-γ could strengthen C/EBPα's function. Expressions of C/EBPα and PPAR-γ were both negatively related with FOXC1 in human HCC tissue. Confocal displayed that C/EBPα was co-located with FOXC1 in HepG2 cells. C/EBPα could bind to FOXC1 promoter by ChIP. Luciferase activity detection exhibited that C/EBPα could inhibit FOXC1 promoter activity, especially FOXC1 promoter from -600 to -300 was the critical binding site. Only PPAR-γ couldn't influence luciferase activity but strengthen inhibited effect of C/EBPα. Further, the Co-IP displayed that PPAR-γ could bind to C/EBPα. When C/EBPα and PPAR-γ was both high expressed, cell proliferation, migration, invasion and colony information were inhibited enormously. C/EBPα plasmid combined with or without PPAR-γ agonist MDG548 treatment exhibited a strong tumor inhibition and FOXC1 suppression in mice. CONCLUSION: Our data establish C/EBPα targeting FOXC1 as potential determinant in the HCC, which supplies a new pathway to treat HCC. However, PPAR-γ has no effect on FOXC1 expression.

19.
Chem Pharm Bull (Tokyo) ; 67(9): 1006-1014, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474723

RESUMO

Chlorogenic acid (CGA) has been considered as one of important active components in a number of medicinal herbs. Recently our group demonstrated that caffeoyl salicylate scaffold derived from CGA can be employed for the development of novel anti-inflammatory agents. The most active compound D104 can be a very promising starting point for the further structural optimization. A series of novel caffeoyl salicylate analogs were designed, synthesized, and evaluated by preliminary biological evaluation. The obtained results showed that the two compounds B12 and B13 can not only inhibit production of nitric oxide (NO) in RAW264.7 cells induced by lipopolysaccharides (LPS) effectively, but also have high safety in in vitro cytotoxic test, which could be comparable with D104. Molecular docking study on the peroxisome proliferator-activated receptor γ (PPARγ) protein revealed that compounds B12 and B13 can follow the same binding mode with D104, and the carboxyl group of caffeoyl salicylate scaffold might play a key role in the interaction with protein target, which implied the carboxyl group should be retained in the further optimization.


Assuntos
Ácido Clorogênico/química , Óxido Nítrico/metabolismo , Ácido Salicílico/química , Células A549 , Animais , Sítios de Ligação , Sobrevivência Celular/efeitos dos fármacos , Ácido Clorogênico/farmacologia , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , PPAR gama/química , PPAR gama/metabolismo , Estrutura Terciária de Proteína , Células RAW 264.7
20.
Cancer Sci ; 110(11): 3543-3552, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31541611

RESUMO

Poly ADP-ribose polymerase inhibitors (PARPi) have shown promising therapeutic efficacy in triple-negative breast cancer (TNBC) patients. However, resistance ultimately develops, preventing a curative effect from being attained. Extensive investigations have indicated the diversity in the mechanisms underlying the PARPi sensitivity of breast cancer. In this study, we found that DNA damage binding protein 2 (DDB2), a DNA damage-recognition factor, could protect TNBC cells from PARPi by regulating DNA double-strand break repair through the homologous recombination pathway, whereas the depletion of DDB2 sensitizes TNBC cells to PARPi. Furthermore, we found that DDB2 was able to stabilize Rad51 by physical association and disrupting its ubiquitination pathway-induced proteasomal degradation. These findings highlight an essential role of DDB2 in modulating homologous recombination pathway activity and suggest a promising therapeutic target for TNBC.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA