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1.
J Proteome Res ; 23(1): 449-464, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38109854

RESUMO

Cancer's high incidence and death rate jeopardize human health and life, and it has become a global public health issue. Some members of NPCs have been studied in a few cancers, but comprehensive and prognostic analysis is lacking in most cancers. In this study, we used the Cancer Genome Atlas (TCGA) data genomics and transcriptome technology to examine the differential expression and prognosis of NPCs in 33 cancer samples, as well as to investigate NPCs mutations and their effect on patient prognosis and to evaluate the methylation level of NPCs in cancer. The linked mechanisms and medication resistance were subsequently investigated in order to investigate prospective tumor therapy approaches. The relationships between NPCs and immune infiltration, immune cells, immunological regulatory substances, and immune pathways were also investigated. Finally, the LUAD and KICH prognostic prediction models were built using univariate and multivariate COX regression analysis. Additionally, the mRNA and protein levels of NPCs were also identified.


Assuntos
Neoplasias Pulmonares , Neoplasias , Humanos , Estudos Prospectivos , Genômica , Análise Multivariada , Mutação , Neoplasias/genética , Prognóstico , Proteína C1 de Niemann-Pick , Proteínas de Transporte Vesicular , Proteínas de Membrana Transportadoras
2.
Anal Chem ; 96(40): 15880-15887, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39312212

RESUMO

Ovarian cancer detection has traditionally relied on a multistep process that includes biopsy, tissue staining, and morphological analysis by experienced pathologists. While widely practiced, this conventional approach suffers from several drawbacks: it is qualitative, time-intensive, and heavily dependent on the quality of staining. Mid-infrared (MIR) hyperspectral photothermal imaging is a label-free, biochemically quantitative technology that, when combined with machine learning algorithms, can eliminate the need for staining and provide quantitative results comparable to traditional histology. However, this technology is slow. This work presents a novel approach to MIR photothermal imaging that enhances its speed by an order of magnitude. This method resolves the longstanding trade-off between imaging resolution and data collection speed, enabling the reconstruction of high-quality, high-resolution images from undersampled data sets and achieving a 10X improvement in data acquisition time. We assessed the performance of our sparse imaging methodology using a variety of quantitative metrics, including mean squared error (MSE), structural similarity index (SSIM), and tissue subtype classification accuracies, employing both random forest and convolutional neural network (CNN) models, accompanied by Receiver Operating Characteristic (ROC) curves. Our statistically robust analysis, based on data from 100 ovarian cancer patient samples and over 65 million data points, demonstrates the method's capability to produce superior image quality and accurately distinguish between different gynecological tissue types with segmentation accuracy exceeding 95%. Our work demonstrates the feasibility of integrating rapid MIR hyperspectral photothermal imaging with machine learning in enhancing ovarian cancer tissue characterization, paving the way for quantitative, label-free, automated histopathology.


Assuntos
Espectrofotometria Infravermelho , Humanos , Feminino , Espectrofotometria Infravermelho/métodos , Imageamento Hiperespectral , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Neoplasias dos Genitais Femininos/diagnóstico por imagem , Neoplasias dos Genitais Femininos/patologia , Aprendizado de Máquina
3.
Small ; 20(14): e2306402, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37992239

RESUMO

Photodynamic therapy (PDT) is extensively investigated for tumor therapy in the clinic. However, the efficacy of PDT is severely limited by the tissue penetrability of light, short effective half-life and radius of reactive oxygen species (ROS), and the weak immunostimulatory effect. In this study, a glutathione (GSH)-activatable nano-photosensitizer is developed to load with arachidonic acid (AA) and camouflage by erythrocyte membrane, which serves as a laser-ignited lipid peroxidation nanoamplifier (MAR). The photosensitive effect of MAR is recovered accompanied by the degradation in the tumor microenvironment and triggers the peroxidation of AA upon laser excitation. Interestingly, it aggravates the propagation of ferroptosis among cancer cells by driving the continuous lipid peroxidation chain reactions with the participation of the degradation products, ferrous ions (Fe2+), and AA. Consequently, even the deep-seated tumor cells without illumination also undergo ferroptosis owing to the propagation of ferroptotic signal. Moreover, the residual tumor cells undergoing ferroptosis still maintain high immunogenicity after PDT, thus continuously triggering sufficient tumor-associated antigens (TAAs) release to remarkably promote the anti-tumor immune response. Therefore, this study will provide a novel "all-in-one" nano-photosensitizer that not only amplifies the damaging effect and expands the effective range of PDT but also improves the immunostimulatory effect after PDT.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Peroxidação de Lipídeos , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Glutationa/metabolismo , Linhagem Celular Tumoral
4.
Dig Dis Sci ; 69(3): 1035-1054, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38282187

RESUMO

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a serious liver disease worldwide, and its pathogenesis is complicated. AIMS: This study investigated the potential role of FANCA in the advancement and prognosis of LIHC. METHODS: Public databases, quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot (WB) and immunohistochemistry (IHC) were employed to measure FANCA expression between tumor and normal samples. The relationship between FANCA expression and prognosis of LIHC patients were examined. Functional enrichment of FANCA-related genes was performed. Furthermore, univariate and multivariate analyses were conducted to determine the independent prognosis value of FANCA in LIHC. Finally, influence of FANCA knockout on the proliferation, migration, and invasion of HepG2 cell was validated with cloning formation, CCK8, and Transwell assays. RESULTS: Expression analysis presented that FANCA had high expression level in LIHC tissues and cells. Receiver operating characteristic (ROC) curve analysis showed that FANCA was of great diagnosis value in LIHC. Clinicopathological analysis revealed that FANCA was significantly greater expressed in the advanced stage than in the early stage of LIHC. Univariate, multivariate, and Kaplan-Meier survival analysis confirmed that high expression of FANCA was strongly associated with poor survival of LIHC patients. In addition, high level of FANCA in LIHC showed a negative association with immunoinfiltrated B cells, T cells, and stromal scores. Moreover, Knockout of FANCA significantly inhibited HepG2 cell proliferative activity, migration, and invasion ability. CONCLUSIONS: Our data revealed that high level of FANCA was closely associated with LIHC malignant progression, suggesting its potential utility as a diagnostic, predictive indicator, and therapeutic target.


Assuntos
Carcinoma Hepatocelular , Anemia de Fanconi , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Western Blotting , Prognóstico , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética
5.
J Environ Manage ; 370: 122391, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39244929

RESUMO

The recovery and upcycling of metals from electronic waste into functional materials for wastewater treatment is a win-win strategy for simultaneously realizing electronic waste recycling and wastewater purification. This study focused on converting Cu from waste printed boards (PCBs), a common Cu-rich electronic waste, into CuFe2O4 supported on a mesoporous carbon framework (PCFT) with the assistance of Fe3+ and tannic acid (TA). Compared to the PCF prepared without TA, the resulting PCFT exhibited excellent magnetic properties, high crystallinity, lower interfacial transfer resistance, more abundant oxygen vacancies (OV), and lower metal leaching. Moreover, PCFT can serve as a superior heterogeneous catalyst to activate peroxymonosulfate to remove reactive brilliant blue KN-R from wastewater, and its catalytic activity was markedly higher than that of CFT synthesized with Cu(NO3)2·3H2O, which may be due to its higher specific surface area and more abundant OV. The combined results of scavenging experiments, electron paramagnetic resonance analysis, and electrochemical measurements implied that both radical and nonradical processes promoted the elimination of KN-R; however, •OH and SO4•- were not the major contributors. Furthermore, the PCFT exhibited high adaptability to pH and water matrices, confirming its practical application potential. These findings provide a novel strategy for the upcycling of metals from electronic waste.

6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(1): 47-51, 2024 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-38171559

RESUMO

OBJECTIVE: To delineate a deletional mutation of the HLA-B gene in a Chinese pedigree. METHODS: A female patient with acute myeloid leukemia who had visited Liuzhou People's Hospital in April 2022 was selected as the study subject. Routine human leukocyte antigen (HLA) was determined by using PCR-sequence specific oligonucleotide polymorphism (PCR-SSOP) and PCR-sequence-based typing (PCR-SBT) methods. Next generation sequencing (NGS) was used to validate the candidate variant in the HLA-B gene. RESULTS: The PCR-SBT and SSOP results for the HLA-B locus were inconsistent for the patient and her daughter. The SSOP results of the two individuals were HLA-B*35:01, 40:02 and HLA-B*35:01, 40:01, respectively. However, the PCR-SBT results has indicated a mismatch with the nearest HLA-B*35:01 at exon 4. NGS results showed that the HLA-B*35:01 had a 9 bp deletion in the intron 5. The patient's husband was HLA-B*40:01, 58:01, which was normal. CONCLUSION: The variant in intron 5 of the HLA-B gene in this pedigree has mapped to a primer-binding region for the SBT reagent, which has affected the accuracy of PCR-SBT results.


Assuntos
Antígenos HLA , Antígenos HLA-B , Humanos , Feminino , Alelos , Linhagem , Antígenos HLA/genética , Antígenos HLA-B/genética , China , Teste de Histocompatibilidade/métodos , Análise de Sequência de DNA/métodos
7.
Funct Integr Genomics ; 23(3): 264, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37541978

RESUMO

Liver cancer is a cunning malignancy with a high incidence and mortality rate among cancers worldwide. The NPC gene family members (NPCs: NPC1, NPC2, and NPC1L1) are closely linked to the development of multiple cancers, but their role in liver cancer remains unclear. As a result, we must investigate their functions in liver hepatocellular carcinoma (LIHC). NPCs were significantly differentially expressed between normal and LIHC tissues, with a high mutation frequency in LIHC. The ROC curve analysis revealed that NPC1/NPC2 had high diagnostic and prognostic values in LIHC. NPC1 expression was also found to be negatively correlated with its methylation level. The differentially expressed genes between high and low NPC1 expression groups in LIHC were mainly related to channel activity, transporter complexes, and plasma membrane adhesion molecules. Additionally, NPC1 expression was significantly associated with multiple immune cells and immunization checkpoints. It was hypothesized that a TUG1/SNHG4-miR-148a-3p-NPC1 regulatory axis is associated with hepatocarcinogenesis. Finally, the protein expression of NPC1 in LIHC tissues and paraneoplastic tissues was detected, and NPC1-knockdown HepG2 cells (NPC1KO) inhibited the proliferation, migration, and invasion. This study helped to identify new prognostic markers and potential immunotherapeutic targets for LIHC and revealed the molecular mechanisms underlying NPC1 regulation in LIHC. The NPCs play a key role in the prognosis and diagnosis of LIHC and may be an important indicator for LIHC prognosis and diagnosis; NPC1 might be a potential therapeutic target in LIHC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Prognóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Multiômica
8.
Analyst ; 148(12): 2699-2708, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37218522

RESUMO

Mid-infrared spectroscopic imaging (MIRSI) is an emerging class of label-free techniques being leveraged for digital histopathology. Modern histopathologic identification of ovarian cancer involves tissue staining followed by morphological pattern recognition. This process is time-consuming and subjective and requires extensive expertise. This paper presents the first label-free, quantitative, and automated histological recognition of ovarian tissue subtypes using a new MIRSI technique. This optical photothermal infrared (O-PTIR) imaging technique provides a 10× enhancement in spatial resolution relative to prior instruments. It enables sub-cellular spectroscopic investigation of tissue at biochemically important fingerprint wavelengths. We demonstrate that the enhanced resolution of sub-cellular features, combined with spectroscopic information, enables reliable classification of ovarian cell subtypes achieving a classification accuracy of 0.98. Moreover, we present a statistically robust analysis from 78 patient samples with over 60 million data points. We show that sub-cellular resolution from five wavenumbers is sufficient to outperform state-of-the-art diffraction-limited techniques with up to 235 wavenumbers. We also propose two quantitative biomarkers based on the relative quantities of epithelia and stroma that exhibit efficacy in early cancer diagnosis. This paper demonstrates that combining deep learning with intrinsic biochemical MIRSI measurements enables quantitative evaluation of cancerous tissue, improving the rigor and reproducibility of histopathology.


Assuntos
Aprendizado Profundo , Neoplasias Ovarianas , Humanos , Feminino , Reprodutibilidade dos Testes , Espectrofotometria Infravermelho , Diagnóstico por Imagem , Neoplasias Ovarianas/diagnóstico
9.
Biochem Genet ; 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658254

RESUMO

Metabolites are important indicators of cancer and mutations in genes involved in amino acid metabolism may influence tumorigenesis. Immunotherapy is an effective cancer treatment option; however, its relationship with amino acid metabolism has not been reported. In this study, RNA-seq data for 371 liver cancer patients were acquired from TCGA and used as the training set. Data for 231 liver cancer patients were obtained from ICGC and used as the validation set to establish a gene signature for predicting liver cancer overall survival outcomes and immunotherapeutic responses. Four reliable groups based on 132 amino acid metabolism-related DEGs were obtained by consistent clustering of 371 HCC patients and a four-gene signature for prediction of liver cancer survival outcomes was developed. Our data show that in different clinical groups, the overall survival outcomes in the high-risk group were markedly low relative to the low-risk group. Univariate and multivariate analyses revealed that the characteristics of the 4-gene signature were independent prognostic factors for liver cancer. The ROC curve revealed that the risk characteristic is an efficient predictor for 1-, 2-, and 3-year HCC survival outcomes. The GSVA and KEGG pathway analyses revealed that high-risk score tumors were associated with all aspects of the degree of malignancy in liver cancer. There were more mutant genes and greater immune infiltrations in the high-risk groups. Assessment of the three immunotherapeutic cohorts established that low-risk score patients significantly benefited from immunotherapy. Then, we established a prognostic nomogram based on the TCGA cohort. In conclusion, the 4-gene signature is a reliable diagnostic marker and predictor for immunotherapeutic efficacy.

10.
BMC Plant Biol ; 22(1): 256, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35606719

RESUMO

BACKGROUND: The adverse effects of climate change on crop production are constraining breeders to develop high-quality environmentally stable varieties. Hence, efforts are being made to identify key genes that could be targeted for enhancing crop tolerance to environmental stresses. ERF transcription factors play an important role in various abiotic stresses in plants. However, the roles of the ERF family in abiotic stresses tolerance are still largely unknown in sesame, the "queen" of oilseed crops. RESULTS: In total, 114 sesame ERF genes (SiERFs) were identified and characterized. 96.49% of the SiERFs were distributed unevenly on the 16 linkage groups of the sesame genome. The phylogenetic analysis with the Arabidopsis ERFs (AtERFs) subdivided SiERF subfamily proteins into 11 subgroups (Groups I to X; and VI-L). Genes in the same subgroup exhibited similar structure and conserved motifs. Evolutionary analysis showed that the expansion of ERF genes in sesame was mainly induced by whole-genome duplication events. Moreover, cis-acting elements analysis showed that SiERFs are mostly involved in environmental responses. Gene expression profiles analysis revealed that 59 and 26 SiERFs are highly stimulated under drought and waterlogging stress, respectively. In addition, qRT-PCR analyses indicated that most of SiERFs are also significantly up-regulated under osmotic, submerge, ABA, and ACC stresses. Among them, SiERF23 and SiERF54 were the most induced by both the abiotic stresses, suggesting their potential for targeted improvement of sesame response to multiple abiotic stresses. CONCLUSION: This study provides a comprehensive understanding of the structure, classification, evolution, and abiotic stresses response of ERF genes in sesame. Moreover, it offers valuable gene resources for functional characterization towards enhancing sesame tolerance to multiple abiotic stresses.


Assuntos
Arabidopsis , Sesamum , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sesamum/metabolismo , Estresse Fisiológico/genética
11.
J Environ Manage ; 317: 115379, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35751236

RESUMO

The construction of cascade reservoirs increases eutrophication and exacerbates algal blooms and thus threatens water quality. Previous studies on the microalgae in reservoir have mainly focused on the spatio-temporal patterns of surface microalgae communities at the horizontal scale, while few studies have simultaneously considered the successions of microalgae in vertical profiles including the sediments and the effects of the nutrients release and microalgae in sediments on microalgae in upper waters. In this study, we investigated the effects of microalgae and physico-chemical parameters in waters and sediments on the successions of vertical microalgae communities in Xipi Reservoir, Southeast China. The seasonal variations in microalgae compositions decreased gradually from the surface water (the dominance of Cryptophyta and Chlorophyta in spring, Chlorophyta and Cyanophyta in summer, and relatively uniform in autumn and winter) to the sediment (the dominance of Bacillariophyta throughout the year), which was influenced by the variations of physico-chemical factors in different layers. The spatio-temporal variations in microalgae communities in waters was attributing to not only the heterogeneities of the stratification, and the physico-chemical factors such as water temperature, pH, and nutrient concentrations, especially for phosphorus in the water column, but also the combinations of phosphorus release and microalgae composition in sediments. Environmental changes would be especially problematic for microalgae groups such as Cryptophyta, Dinophyta and Chlorophyta that were sensitive to the changes of temperature and nutrients. Our results are helpful for an extensive understanding of the dynamics of microalgae communities in reservoir, and contribute to reservoir management for ensuring the safety of drinking water.


Assuntos
Clorófitas , Microalgas , China , Monitoramento Ambiental , Eutrofização , Nitrogênio/análise , Fósforo/análise , Fitoplâncton , Estações do Ano
12.
Cancer Cell Int ; 21(1): 356, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233686

RESUMO

BACKGROUND: In view of the fact that peripheral blood parameters have been reported as predictors of immunotherapy to various cancers, this study aimed to determine the predictors of response to anti-programmed death-1 (anti-PD-1) therapy in patients with esophageal squamous cell carcinoma (ESCC) from peripheral blood parameters. METHODS: A retrospective analysis was conducted to investigate the predictive value of peripheral blood parameters including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) in the response to anti-PD-1 antibody treatment. 119 ESCC patients receiving combined treatment including anti-PD-1 antibody were enrolled in this study. RESULTS: The median progression-free survival (PFS) of all ESCC patients was 3.73 months. PFS rate in ESCC patients with low NLR at 6 weeks post treatment was higher than patients with high NLR (HR = 2.097, 95% CI 0.996-4.417, P = 0.027). However, PFS rate in ESCC patients with low NLR at baseline (HR = 1.060, 95% CI 0.524-2.146, P = 0.869) or 3 weeks post treatment (HR = 1.293, 95% CI 0.628-2.663, P = 0.459) was comparable with high NLR. And no statistically different was found in PFS rate between low PLR and high PLR at baseline (HR = 0.786, 95% CI 0.389-1.589, P = 0.469), 3 weeks post treatment (HR = 0.767, 95% CI 0.379-1.552, P = 0.452) or 6 weeks post treatment (HR = 1.272, 95% CI 0.624-2.594, P = 0.488) in ESCC patients. PFS rate was also comparable between low MLR and high MLR at baseline (HR = 0.826, 95% CI 0.408-1.670, P = 0.587), 3 weeks post treatment (HR = 1.209, 95% CI 0.590-2.475, P = 0.580) or 6 weeks post treatment (HR = 1.199, 95% CI 0.586-2.454, P = 0.596). PFS rate was similar between patients with low SII and high SII at baseline (HR = 1.120, 95% CI 0.554-2.264, P = 0.749), 3 weeks post treatment (HR = 1.022, 95% CI 0.500-2.089, P = 0.951) and 6 weeks post treatment (HR = 1.759, 95% CI 0.851-3.635, P = 0.097). CONCLUSIONS: NLR at 6 weeks post treatment is a predictor of the response to anti-PD-1 treatment in patients with ESCC.

13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(3): 282-285, 2021 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-33751543

RESUMO

OBJECTIVE: To delineate the characteristics of a novel HLA-DQB1 allele identified during routine HLA matching in a leukemia family. METHODS: The mother and brother of the patient were subjected to PCR sequence-specific oligonucleotide probe (SSOP), PCR sequence-based typ1ing (SBT), as well as next-generation sequencing (NGS). RESULTS: PCR-SBT revealed that the patient's mother and brother's HLA-DQB1 sequences did not fully match with any known allele combination. NGS revealed that the novel allele has differed from the closest matched DQB1*03:02 with a T>G substitution at position 233 in exon 2, which resulted in substitution of Valine at codon 46 by Glycine. Pedigree analysis confirmed that the novel HLA-DQB1 allele was inherited from his mother. CONCLUSION: A novel HLA-DQB1 allele has been identified through next generation sequencing and was officially named as HLA-DQB1*03:362 by the World Health Organization HLA Factor Nomenclature Committee.


Assuntos
Cadeias beta de HLA-DQ , Nucleotídeos , Análise de Sequência de DNA , Alelos , Sequência de Bases , Cadeias beta de HLA-DQ/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(6): 681-684, 2020 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-32472552

RESUMO

OBJECTIVE: To verify a HLA-DQB1*03:90N allele and method to improve the accuracy of HLA typing. METHODS: A total of 2265 hematopoietic stem cell donors from Shenzhen Branch of China Marrow Donor Program in 2018 were initially detected by a PCR sequence-specific oligonucleotide probe (SSOP) method. Among these, a rare HLA-DQB1 allele was identified by sequence-based tying (SBT) and Ion Torrent S5 next generation sequencing (NGS). RESULTS: The SSOP typing result suggested the HLA-DQB1 to be a rare allele, while an insertion and a deletion was suspected in its exon 2 by SBT, which were confirmed by NGS as DQB1*03:90N and DQB1*06:01, respectively. CONCLUSION: Rare alleles suspected by the SSOP method should be verified by other methods to ensure the accuracy of HLA genotyping. Rare alleles formed by deletions can be detected by NGS with accuracy.


Assuntos
Cadeias beta de HLA-DQ/genética , Alelos , China , Teste de Histocompatibilidade , Humanos
15.
Anticancer Drugs ; 30(10): 1038-1047, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31274517

RESUMO

Triple negative breast cancer (TNBC) has very poor prognosis and no efficacious therapeutic options due to the absence of a validated molecular target. Therefore, novel therapeutic strategies against TNBC are urgently needed. Our team synthesized and screened a series of compounds derived from Rhein, of which 4F was selected for further analysis based on its ability to produce the vacuolated appearance of cells. Using Cell counting kit-8 assay, colony-formation assay, cell apoptosis and cell cycle assay, we compared the antitumor effects of 4F, Rhein and Cisplatin on a TNBC cell line MDA-MB-231 in vitro. The vacuoles in MDA-MB-231 cells were observed and analyzed by hematoxylin-eosin staining and transmission electron microscopy. Autophagy and apoptosis-related proteins including p62, Microtubule Light Chain 3 (LC3), Beclin-1 and Caspase-3 were determined by western blot. The tandem mRFP-GFP-LC3 Lentivirus was used for monitoring the maturation step of autophagosomes. Our data revealed that 4F had lower cytotoxicity to normal breast cell line MCF-10A as compared with positive drug Doxorubicin. Although 4F had better cytotoxicity than Rhein, it had no influence on cells apoptosis in 4F-treated cells. Accumulation of autolysosomes and autophagosomes was observed in 4F-treated MDA-MB-231 cells, accompanied by increased level of Beclin-1 protein. Enhanced autophagic flux was verified by higher ratio of LC3-II/LC3-I, the degradation of p62 protein and alteration in red and green fluorescence puncta. These findings suggested that the process of MDA-MB-231 cell death induced by 4F seemed rely mainly on autophagy rather than apoptosis. 4F may be an alternative drug candidate against TNBC and merits more exploration.


Assuntos
Antraquinonas/química , Antraquinonas/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Morte Celular Autofágica/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Estrutura Molecular , Neoplasias de Mama Triplo Negativas/patologia , Vacúolos/efeitos dos fármacos
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(5): 439-442, 2019 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-31030428

RESUMO

OBJECTIVE: To assess the association of KIR/HLA alleles with hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) infection among ethnic Han Chinese patients from southern China. METHODS: For 95 patients with HCC and 171 healthy controls, the genotype of HLA-C alleles was determined with a PCR sequence-specific oligonucleotides typing method on an Illumina GenDx NGSgo platform. Genotypes comprised of HLA-C and KIR gene alleles were also subjected to statistical analysis. RESULTS: In total 16 KIR genes (2DL2, 2DS2, 2DS3, 2DS5, 3DS1, 2DS1, 2DL5, 2DS4, 3DL1, 3DP1, 2DL3, 2DP1, 3DL3, 2DL1, 3DL2 and 2DL4) were discovered in the two groups. The frequencies of KIR2DL3 alleles and combinational genotypes of KIR2DL3/HLA-C1C2 were significantly lower in the patient group compared with the controls (0.9368 vs. 0.9883, χ²>3.84; P<0.05, OR = 0.1; 0.0112 vs. 0.2663, χ²>3.84; P<0.05, RR = 0.03). The frequency of HLA-C2C2 genotype of the patient group was significantly lower than that of the controls (0.0316 vs. 0.2690, P<0.05, RR = 0.09), while the frequency of HLA-C1C2 genotype was significantly higher than that of the controls (0.2316 vs. 0.0058, P<0.05, RR = 51.23). CONCLUSION: Above results suggested that the KIR2DL3 allele is associated with lower risk for HCC. There may be individual difference in patients with HCC and HBV infection but various combinations of KIR/HLA alleles.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Alelos , Carcinoma Hepatocelular/genética , China , Frequência do Gene , Genótipo , Humanos , Neoplasias Hepáticas/genética , Polimorfismo Genético , Receptores KIR
18.
World J Surg Oncol ; 15(1): 219, 2017 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-29233162

RESUMO

BACKGROUND: Sarcomatoid hepatocellular carcinoma (SHC) is a rare malignant hepatic tumor. Recurrent interventional therapies such as transcatheter arterial chemo-embolization (TACE), radiofrequency ablation (RFA), and percutaneous ethanol injection have been reported previously utilized in a majority of SHC cases. To date, the exact pathogenic mechanisms underlying sarcomatoid transformation of hepatocellular carcinoma (HCC) remain unknown. CASE PRESENTATION: In this study, we report a 68-year-old female SHC patient admitted to our hospital due to discrete abdominal distention for more than 20 days. Abdominal computed tomography (CT) with tri-phase enhancement revealed portal vein tumor thrombi (PVTT) and a left hepatic lobe lesion measuring 110.0 mm × 160.0 mm. The patient subsequently underwent liver resection, after which pathological examination revealed proliferation of spindle-shaped SHC cells. A sarcomatoid, T4 stage carcinoma was eventually diagnosed. Forty-seven days after the operation, tri-phase enhanced CT detected extensive lesions in the liver, spleen, peritoneum, omentum majus, and mesentery, indicating SHC recurrence and metastases. Combination chemotherapy with pirarubicin and cisplatin was initiated for 1 cycle, but terminated due to resultant severe myelosuppression and medication intolerance. The patient was lost to therapy after 3 months of follow-up. CONCLUSIONS: This case is unique because of hepatitis C virus infection. We should consider the possibility of this disease in patients with atypical clinical presentation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/terapia , Carcinossarcoma/terapia , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinossarcoma/diagnóstico por imagem , Quimioterapia Adjuvante/métodos , Feminino , Hepatectomia/métodos , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Prognóstico , Tomografia Computadorizada por Raios X
20.
Chem Biomed Imaging ; 2(9): 651-658, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39328427

RESUMO

Hyperspectral photothermal mid-infrared spectroscopic imaging (HP-MIRSI) is an emerging technology with promising applications in cervical cancer diagnosis and quantitative, label-free histopathology. This study pioneers the application of HP-MIRSI to the evaluation of clinical cervical cancer tissues, achieving excellent tissue type segmentation accuracy of over 95%. This achievement stems from an integrated approach of optimized data acquisition, computational data reconstruction, and the application of machine learning algorithms. The results are statistically robust, drawing from tissue samples of 98 cervical cancer patients and incorporating over 40 million data points. Traditional cervical cancer diagnosis methods entail biopsy, staining, and visual evaluation by a pathologist. This process is qualitative, subject to variations in staining and subjective interpretations, and requires extensive tissue processing, making it costly and time-consuming. In contrast, our proposed alternative can produce images comparable to those from histological analyses without the need for staining or complex sample preparation. This label-free, quantitative method utilizes biochemical data from HP-MIRSI and employs machine-learning algorithms for the rapid and precise segmentation of cervical tissue subtypes. This approach can potentially transform histopathological analysis by offering a more accurate and label-free alternative to conventional diagnostic processes.

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