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1.
Antonie Van Leeuwenhoek ; 117(1): 81, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777900

RESUMO

A Gram-stain-negative, aerobic, non-motile, catalase- and oxidase-positive, pale orange, rod-shaped strain EF6T, was isolated from a natural wetland reserve in Hebei province, China. The strain grew at 25-37 °C (optimum, 30 °C), pH 5-9 (optimum, pH 7), and in the presence of 1.0-4.0% (w/v) NaCl (optimum, 2%). A phylogenetic analysis based on 16S rRNA gene sequence revealed that strain EF6T belongs to the genus Paracoccus, and the closest members were Paracoccus shandongensis wg2T with 98.1% similarity, Paracoccus fontiphilus MVW-1 T (97.9%), Paracoccus everestensis S8-55 T (97.7%), Paracoccus subflavus GY0581T (97.6%), Paracoccus sediminis CMB17T (97.3%), Paracoccus caeni MJ17T (97.0%), and Paracoccus angustae E6T (97.0%). The genome size of strain EF6T was 4.88 Mb, and the DNA G + C content was 65.3%. The digital DNA-DNA hybridization, average nucleotide identity, and average amino acid identity values between strain EF6T and the reference strains were all below the threshold limit for species delineation (< 32.8%, < 88.0%, and < 86.7%, respectively). The major fatty acids (≥ 5.0%) were summed feature 8 (86.3%, C18:1 ω6c and/or C18:1 ω7c) and C18:1 (5.0%) and the only isoprenoid quinone was Q-10. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids, five unidentified phospholipids, and an unidentified aminolipid. Strain EF6T displays notable resistance to benzoate and selenite, with higher tolerance levels (25 g/L for benzoate and 150 mM for selenite) compared to the closely related species. Genomic analysis identified six benzoate resistance genes (acdA, pcaF, fadA, pcaC, purB, and catA) and twenty selenite resistance and reduction-related genes (iscR, ssuB, ssuD, selA, selD and so on). Additionally, EF6T possesses unique genes (catA, ssuB, and ssuC) absent in the closely related species for benzoate and selenite resistance. Its robust resistance to benzoate and selenite, coupled with its genomic makeup, make EF6T a promising candidate for the remediation of both organic and inorganic pollutants. It is worth noting that the specific resistance phenotypes described above were not reported in other novel species in Paracoccus. Based on the results of biochemical, physiological, phylogenetic, and chemotaxonomic analyses, combined with comparisons of the 16S rRNA gene sequence and the whole genome sequence, strain EF6T is considered to represent a novel species of the genus Paracoccus within the family Rhodobacteraceae, for which the name Paracoccus benzoatiresistens sp. nov. is proposed. The type strain is EF6T (= GDMCC 1.3400 T = JCM 35642 T = MCCC 1K08702T).


Assuntos
Composição de Bases , DNA Bacteriano , Ácidos Graxos , Paracoccus , Filogenia , RNA Ribossômico 16S , Áreas Alagadas , Paracoccus/genética , Paracoccus/classificação , Paracoccus/isolamento & purificação , Paracoccus/metabolismo , Paracoccus/efeitos dos fármacos , RNA Ribossômico 16S/genética , Ácidos Graxos/metabolismo , Ácidos Graxos/química , DNA Bacteriano/genética , China , Selenito de Sódio/metabolismo , Técnicas de Tipagem Bacteriana , Fosfolipídeos/análise , Análise de Sequência de DNA , Hibridização de Ácido Nucleico , Oxirredução , Farmacorresistência Bacteriana
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 342-346, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660834

RESUMO

OBJECTIVE: To observe the clinical efficacy and safety of venetoclax (VEN) combined with azacitidine (AZA) in the treatment of adult acute myeloid leukemia (AML) patients who are unfit for intensive chemotherapy. METHODS: The clinical data of 21 adult patients with unfit AML who were treated with VEN combined with AZA in the Second Hospital of Shanxi Medical University from January 2021 to May 2022 were collected, and the efficacy and safety were analyzed retrospectively. RESULTS: After one course of treatment with VEN and AZA, 16 out of 21 unfit AML patients reached complete remission (CR)/CR with incomplete hematologic recovery (CRi), 2 patients reached partial remission (PR), the overall response rate (ORR) was 85.7%. Among the 16 patients with CR/CRi, 13 achieved minimal residual disease (MRD) negativity. Among the 11 patients with adverse prognosis, 8 achieved CR/CRi. By the deadline of follow-up, the median overall suivival (OS) of the entire cohort was not reached, with 1-year OS rate of 61.7%. The main adverse events of VEN combined with AZA were myelosuppression, gastrointestinal reactions and infections. There were 13 cases of leukopenia, 7 cases of neutropenia, 7 cases of anemia, 4 cases of thrombocytopenia, and these hematologic adverse events were all grade 3-4. There were 11 cases with gastrointestinal reactions and 7 cases with infections. The above adverse events were controllable and tolerable. No tumor lysis syndrome or infection related death occurred. CONCLUSION: VEN combined with AZA can quickly achieve deep remission in adult patients with unfit AML, and it shows a good safety profile.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina , Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Sulfonamidas/administração & dosagem , Azacitidina/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Indução de Remissão , Resultado do Tratamento , Masculino , Adulto , Feminino , Pessoa de Meia-Idade
3.
J Appl Clin Med Phys ; : e14371, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38682540

RESUMO

PURPOSE: To create and evaluate a three-dimensional (3D) Prompt-nnUnet module that utilizes the prompts-based model combined with 3D nnUnet for producing the rapid and consistent autosegmentation of high-risk clinical target volume (HR CTV) and organ at risk (OAR) in high-dose-rate brachytherapy (HDR BT) for patients with postoperative endometrial carcinoma (EC). METHODS AND MATERIALS: On two experimental batches, a total of 321 computed tomography (CT) scans were obtained for HR CTV segmentation from 321 patients with EC, and 125 CT scans for OARs segmentation from 125 patients. The numbers of training/validation/test were 257/32/32 and 87/13/25 for HR CTV and OARs respectively. A novel comparison of the deep learning neural network 3D Prompt-nnUnet and 3D nnUnet was applied for HR CTV and OARs segmentation. Three-fold cross validation and several quantitative metrics were employed, including Dice similarity coefficient (DSC), Hausdorff distance (HD), 95th percentile of Hausdorff distance (HD95%), and intersection over union (IoU). RESULTS: The Prompt-nnUnet included two forms of parameters Predict-Prompt (PP) and Label-Prompt (LP), with the LP performing most similarly to the experienced radiation oncologist and outperforming the less experienced ones. During the testing phase, the mean DSC values for the LP were 0.96 ± 0.02, 0.91 ± 0.02, and 0.83 ± 0.07 for HR CTV, rectum and urethra, respectively. The mean HD values (mm) were 2.73 ± 0.95, 8.18 ± 4.84, and 2.11 ± 0.50, respectively. The mean HD95% values (mm) were 1.66 ± 1.11, 3.07 ± 0.94, and 1.35 ± 0.55, respectively. The mean IoUs were 0.92 ± 0.04, 0.84 ± 0.03, and 0.71 ± 0.09, respectively. A delineation time < 2.35 s per structure in the new model was observed, which was available to save clinician time. CONCLUSION: The Prompt-nnUnet architecture, particularly the LP, was highly consistent with ground truth (GT) in HR CTV or OAR autosegmentation, reducing interobserver variability and shortening treatment time.

4.
Clin Breast Cancer ; 24(3): 191-198, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38368247

RESUMO

PURPOSE: This study was a retrospective and nonrandomized study to assess the safety and reliability of identifying the surgical margin in breast cancer breast-conserving surgery (BCS) by using intraoperative ultrasonic location and specimen mammography instead of traditional intraoperative frozen pathological section. METHODS: Among the patients who underwent BCS from May 2019 to October 2021, according to the different methods of evaluating the intraoperative margin, 104 breast cancer patients were included in the frozen edge group, 53 breast cancer patients were included in the freeze-free group, and the surgeon judged whether extended resection was needed based on the results of pathological section or evaluation of intraoperative ultrasound and mammography. The surgical margins of the two groups were judged by postoperative pathological results as the gold standard. RESULTS: The median waiting pathology results time in the frozen edge group was 64 minutes, while the waiting time in the freeze-free group was 30 minutes, and the difference was statistically significant (P < .0001). The postoperative pathological results showed that the positive rate of the surgical margin in the frozen edge group was 0.96%. The coincidence rate of intraoperative frozen and postoperative pathological results was 99.04%. The coincidence rate between intraoperative mammography and postoperative pathological results was 100%. CONCLUSIONS: In BCS, the method of using intraoperative staining markers combined with mammography to evaluate the resection margin is highly accurate, reliable, economical and convenient, and at the same time reduces the waiting time of the operator during the operation. However, this was not a randomized controlled study, and there was patient selection bias, and its safety needs to be confirmed by long-term follow-up. In the future, it is expected to become the mainstream means of evaluating.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Mastectomia Segmentar/métodos , Secções Congeladas/métodos , Estudos Retrospectivos , Margens de Excisão , Reprodutibilidade dos Testes
5.
Crit Rev Oncol Hematol ; 195: 104269, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272149

RESUMO

Breast cancer is the most frequent malignancy in women. However, in the middle and late stages, some people develop distant metastases, which considerably lower the quality of life and life expectancy. The brain is one of the sites where metastasis frequently happens. According to epidemiological research, brain metastases occur at a late stage in 30-50% of patients with HER2-positive breast cancer, resulting in a poor prognosis. Additionally, few treatments are available for HER2-positive brain metastatic breast cancer, and the mortality rate is remarkable owing to the complexity of the brain's anatomical structure and physiological function. In this review, we described the stages of the brain metastasis of breast cancer, the relationship between the microenvironment and metastatic cancer cells, and the unique molecular and cellular mechanisms. It involves cancer cells migrating, invading, and adhering to the brain; penetrating the blood-brain barrier; interacting with brain cells; and activating signal pathways once inside the brain. Finally, we reviewed current clinically used treatment approaches for brain metastasis in HER2-positive breast cancer; summarized the traditional treatment, targeted treatment, immunotherapy, and other treatment modalities; compared the benefits and drawbacks of each approach; discussed treatment challenges; and emphasized the importance of identifying potential targets to improve patient survival rates and comprehend brain metastasis in breast cancer.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Feminino , Humanos , Encéfalo/patologia , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Prognóstico , Qualidade de Vida , Receptor ErbB-2/genética , Microambiente Tumoral
6.
Clin Transl Oncol ; 26(6): 1395-1406, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38190033

RESUMO

PURPOSE: This study aimed to identify the impact of epidermal growth factor receptor (EGFR) T790M mutations on clinical characteristics and prognosis. METHODS: Retrospective analyses were conducted on the differences on clinicopathological features and prognosis between primary and acquired T790M mutations. Subgroup analyses were performed for primary T790M coexisting with other mutations. RESULTS: Patients with primary T790M mutations showed a 60.53% (23/38) incidence of concurrent L858R mutations, 18.42% (7/38) for 19del mutations and a 21.05% (8/38) occurrence of brain metastases. Conversely, those with acquired T790M mutations demonstrated respective frequencies of 36.53% (61/167), 58.68% (98/167) and 44.31% (74/167), with all comparisons yielding p < 0.05. The median overall survival differed significantly between the two groups, with a duration of 33 months for patients with primary T790M mutations as compared to 48 months for those with acquired mutations (p = 0.030). Notably, among patients with L858R co-mutations, when treated with third-generation EGFR-TKIs, those with acquired T790M mutations experienced a significantly prolonged median time to treatment failure compared to those with primary mutations (17 months vs. 9 months, p = 0.009). CONCLUSION: Patients with primary T790M have unique molecular features and had worse prognosis compared with acquired T790M. Resistance to third-generation EGFR-TKIs seems to be associated with the presence of EGFR co-mutations.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Humanos , Receptores ErbB/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Prognóstico , Pessoa de Meia-Idade , Idoso , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/mortalidade , Idoso de 80 Anos ou mais , Inibidores de Proteínas Quinases/uso terapêutico , Taxa de Sobrevida
7.
Pestic Biochem Physiol ; 198: 105728, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38225082

RESUMO

BACKGROUND: Omphalia lapidescens is a saprophytic and parasitic fungus belonging to the Polypora genus of Tricholomataceae. It has repellent, insecticidal, anti-inflammatory and immunomodulatory effects. RESULT: This study found that the extract of O. lapidescens had significant anti-TMV activity, and the main active component was homopolysaccharide LW-1 by Bioassay-guided fractionation. LW-1 is a glucan with ß-(1,3) glucoside bond as the main chain and ß-(1,6) glucoside bond as the branch chain, with molecular weight in the range of 172,916-338,827 Da. The protective and inactive efficacies of LW-1(100 mg/L) against TMV were 78.10% and 48.20%, but had no direct effect on the morphology of TMV particles. The results of mechanism of action showed that LW-1 induced the increase of the activity of defense enzymes such as POD, SOD and PAL in Nicotiana glutinosa. The overexpression of resistance genes such as NPR1, PR1 and PR5, and the increase of SA content. Further transcriptome sequencing showed that LW-1 activated MAPK signaling pathway, plant-pathogen interaction pathway and glucosinolide metabolic pathway in Arabidopsis thaliana. Besides, LW-1 induced crops resistance against plant pathogenic fungi. CONCLUSION: Taken together, the anti-TMV mechanism of LW-1 was to activate MAPK signaling pathway, inducing overexpression of resistance genes, activating plant immune system, and improving the synthesis and accumulation of plant defencins such as glucosinolide. LW-1-induced plant disease resistance has the advantages of broad spectrum and long duration, which has the potential to be developed as a new antiviral agent or plant immune resistance inducer.


Assuntos
Arabidopsis , Vírus do Mosaico do Tabaco , Resistência à Doença/genética , Transdução de Sinais , Nicotiana , Glucosídeos , Doenças das Plantas/prevenção & controle , Doenças das Plantas/genética
8.
Int J Biol Macromol ; 258(Pt 2): 128985, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154359

RESUMO

This study aimed to prepare oregano essential oil microcapsules (EOMs) by the active coalescence method using gelatin and sodium alginate as wall materials and oregano essential oil (OEO) as the core material. EOMs were added to the soybean protein isolate (SPI)/sodium carboxymethyl cellulose (CMC) matrix to prepare SPI-CMC-EOM active films, and the physical and chemical features of the active films and EOMs were characterized. The results showed that the microencapsulated OEO could protect its active ingredients. Scanning electron microscopy results showed that EOMs were highly compatible with the film matrix. The solubility of active films decreased upon adding EOMs, and their ultraviolet resistance and thermal stability also improved. When the added amount of EOMs was 5 %, the active films had the best mechanical properties and the lowest water vapor permeability. The active films prepared under this condition had excellent comprehensive performance. Also, adding EOMs considerably enhanced the antioxidant of the active films and endowed them with antibacterial properties. The application of the SPI-CMC-EOM films to A. bisporus effectively delayed senescence and maintained the freshness of the postharvest A. bisporus. This study provided a theoretical foundation for the incorporation of EOMs into active films based on biological materials.


Assuntos
Óleos Voláteis , Origanum , Carboximetilcelulose Sódica/química , Proteínas de Soja/química , Embalagem de Alimentos/métodos , Óleos Voláteis/química , Cápsulas , Sódio
9.
Int J Mol Sci ; 24(22)2023 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-38003411

RESUMO

Bisphenol AF (BPAF) represents a common environmental estrogenic compound renowned for its capacity to induce endocrine disruptions. Notably, BPAF exhibits an enhanced binding affinity to estrogen receptors, which may have more potent estrogenic activity compared with its precursor bisphenol A (BPA). Notwithstanding, the existing studies on BPAF-induced prostate toxicity remain limited, with related toxicological research residing in the preliminary stage. Our previous studies have confirmed the role of BPAF in the induction of ventral prostatic hyperplasia, but its role in the dorsal lobe is not clear. In this study, BPAF (10, 90 µg/kg) and the inhibitor of nuclear transcription factor-κB (NF-κB), pyrrolidinedithiocarbamate (PDTC, 100 mg/kg), were administered intragastrically in rats for four weeks. Through comprehensive anatomical and pathological observations, as well as the assessment of PCNA over-expression, we asserted that BPAF at lower doses may foster dorsal prostatic hyperplasia in rats. The results of IHC and ELISA indicated that BPAF induced hyperplastic responses in the dorsal lobe of the prostate by interfering with a series of biomarkers in NF-κB signaling pathways, containing NF-κB p65, COX-2, TNF-α, and EGFR. These findings confirm the toxic effect of BPAF on prostate health and emphasize the potential corresponding mechanisms.


Assuntos
NF-kappa B , Hiperplasia Prostática , Humanos , Masculino , Ratos , Animais , NF-kappa B/metabolismo , Hiperplasia Prostática/induzido quimicamente , Hiperplasia , Próstata/metabolismo , Receptor alfa de Estrogênio/metabolismo , Transdução de Sinais , Compostos Benzidrílicos/toxicidade
10.
Pestic Biochem Physiol ; 194: 105512, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37532363

RESUMO

The main component of orange peel essential oil is limonene. Limonene is a natural active monoterpene with multiple functions, such as antibacterial, antiseptic and antitumor activity, and has important development value in agriculture. This study found that limonene exhibited excellent anti-tobacco mosaic virus (TMV) bioactivity, with results showing that its protection activity, inactivation activity, and curative activity at 800 µg/mL were 84.93%, 59.28%, and 58.89%, respectively-significantly higher than those of chito-oligosaccharides. A direct effect of limonene on TMV particles was not observed, but limonene triggered the hypersensitive response (HR) in tobacco. Further determination of the induction activity of limonene against TMV demonstrated that it displayed good induction activity at 800 µg/mL, with a value of 60.59%. The results of physiological and biochemical experiments showed that at different treatment days, 800 µg/mL limonene induced the enhancement of defense enzymes activity in tobacco, including of SOD, CAT, POD, and PAL, which respectively increased by 3.2, 4.67, 4.12, and 2.33 times compared with the control (POD and SOD activities reached highest on the seventh day, and PAL and CAT activities reached highest on the fifth day). Limonene also enhanced the relative expression levels of pathogenesis related (PR) genes, including NPR1, PR1, and PR5, which were upregulated 3.84-fold, 1.86-fold and 1.71-fold, respectively. Limonene induced the accumulation of salicylic acid (SA), and increased the relative expression levels of genes related to SA biosynthesis (PAL) and reactive oxygen species (ROS) burst (RBOHB), which respectively increased by 2.76 times and 4.23 times higher than the control. Systemic acquired resistance (SAR) is an important plant immune defense against pathogen infection. The observed accumulation of SA, the enhancement of defense enzymes activity and the high-level expression of defense-related genes suggested that limonene may induce resistance to TMV in tobacco by activating SAR mediated by the SA signaling pathway. Furthermore, the experimental results demonstrated that the expression level of the chlorophyll biosynthesis gene POR1 was increased 1.72-fold compared to the control in tobacco treated with 800 µg/mL limonene, indicating that limonene treatment may increase chlorophyll content in tobacco. The results of pot experiment showed that 800 µg/mL limonene induced plant resistance against Sclerotinia sclerotiorum (33.33%), Phytophthora capsici (54.55%), Botrytis cinerea (50.00%). The bioassay results indicated that limonene provided broad-spectrum and long-lasting resistance to pathogen infection. Therefore, limonene has good development and utilization value, and is expected to be developed into a new botanical-derived anti-virus agent and plant immunity activator in addition to insecticides and fungicides.


Assuntos
Vírus do Mosaico do Tabaco , Limoneno/farmacologia , Ácido Salicílico/metabolismo , Nicotiana , Clorofila/metabolismo , Superóxido Dismutase/metabolismo , Doenças das Plantas/prevenção & controle , Proteínas de Plantas/genética
11.
Bioorg Chem ; 138: 106601, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37224740

RESUMO

Histone deacetylases (HDACs) are responsible for the deacetylation of lysine residues in histone or non-histone substrates, leading to the regulation of many biological functions, such as gene transcription, translation and remodeling chromatin. Targeting HDACs for drug development is a promising way for human diseases, including cancers and heart diseases. In particular, numerous HDAC inhibitors have revealed potential clinical value for the treatment of cardiac diseases in recent years. In this review, we systematically summarize the therapeutic roles of HDAC inhibitors with different chemotypes on heart diseases. Additionally, we discuss the opportunities and challenges in developing HDAC inhibitors for the treatment of cardiac diseases.


Assuntos
Cardiopatias , Neoplasias , Humanos , Histona Desacetilases/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Inibidores de Histona Desacetilases/química , Cardiopatias/tratamento farmacológico , Histonas , Neoplasias/tratamento farmacológico
12.
Front Nutr ; 10: 1091067, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36925958

RESUMO

Diet dictates nutrient availability in the tumor microenvironment, thus affecting tumor metabolic activity and growth. Intrinsically, tumors develop unique metabolic features and are sensitive to environmental nutrient concentrations. Tumor-driven nutrient dependencies provide opportunities to control tumor growth by nutritional restriction or supplementation. This review summarized the existing data on nutrition and pediatric cancers after systematically searching articles up to 2023 from four databases (PubMed, Web of Science, Scopus, and Ovid MEDLINE). Epidemiological studies linked malnutrition with advanced disease stages and poor clinical outcomes in pediatric cancer patients. Experimental studies identified several nutrient dependencies (i.e., amino acids, lipids, vitamins, etc.) in major pediatric cancer types. Dietary modifications such as calorie restriction, ketogenic diet, and nutrient restriction/supplementation supported pediatric cancer treatment, but studies remain limited. Future research should expand epidemiological studies through data sharing and multi-institutional collaborations and continue to discover critical and novel nutrient dependencies to find optimal nutritional approaches for pediatric cancer patients.

13.
J Clin Lab Anal ; 37(4): e24822, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36806318

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) ATB belongs to an active modulator in multiple cancers, but its expression along with potential underlying non-small cell lung cancer (NSCLC) is obscure. Our study aimed to investigate the role and potential mechanism of LncRNA ATB in NSCLC. METHODS: LncRNA ATB expression in NSCLC tissues and cell lines was detected by qRT-PCR. Effects of LncRNA ATB on NSCLC cell proliferation, migration and invasion were assessed by MTS, colony formation and transwell assays. The connection among LncRNA ATB, miR-200b and fibronectin 1 (FN1) was determined by bioformatics prediction and luciferase reporter assay. RESULTS: In this research, upregulation of LncRNA ATB was discovered in NSCLC tissue samples and cell lines. LncRNA ATB was positively related to advanced tumor phase as well as lymph node metastasis. Cell function assays reflected LncRNA ATB expedited NSCLC cells proliferation, migration and invasion. LncRNA ATB promoted fibronectin 1 (FN1) expression via inhibiting miR-200b. Furthermore, LncRNA ATB depletion suppressed NSCLC cells proliferation, migration and invasion, while miR-200b inhibitor or pcDNA-FN1 rescued these effects. CONCLUSION: In summary, our outcomes elucidated that LncRNA ATB/miR-200b axis expedited NSCLC cells proliferation, migration and invasion by up-regulating FN1.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Fibronectinas , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Fibronectinas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
14.
Comb Chem High Throughput Screen ; 26(5): 1030-1041, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35718967

RESUMO

BACKGROUND: Turning the "cold" tumor immune microenvironment into "hot" is a critical issue in cancer treatment today. Hormone receptor-rich breast cancer (HR+ BC) was previously considered immunologically quiescent. OBJECTIVE: This study aims to explore the immunomodulatory effects of endocrine therapy on HR+ BCs. METHODS: The infiltrations and alterations of the tumor immune microenvironment in HR+ BCs before, after 10-14 days, and after three months of neoadjuvant endocrine therapy were computationally analyzed according to MCP-counter, CIBERSORT, xCell algorithms, and gene-set enrichment analysis (GSEA). The primary microarray data were obtained from three HR+ BC gene expression datasets (GSE20181, GSE55374, and GSE59515). Single-sample GSEA of hallmark and immune response gene sets was performed to evaluate the correlation between suspected treatment response and activated immune pathways in tumors. RESULTS: Both immune and stromal cells were specifically recruited into the HR+ BCs who responded to the neoadjuvant endocrine therapy by letrozole. Besides the enhanced infiltrations of immunosurveillance-related cells such as CD8+ T cells, dendritic cells, and the activation of immune response-related signals, the immunosuppressive M2-like macrophages, as well as the expression of immune checkpoint genes like PDCD1, SIRPA, and some HLA genes, were also stimulated in responders. We identified four pretreatment indicators (the intrinsic luminal subtype, the estrogen response early/late pathway, and the epithelial-mesenchymal transition pathway) as potential predictors of both clinical response and the activation of the tumor immune microenvironment post letrozole. CONCLUSION: Neoadjuvant endocrine therapy showed a promising way to convert the immunologically "cold" HR+ BCs into "hot" tumors. This study provides new insights into the application of immunotherapy for HR+ BCs, especially those who respond to endocrine therapy.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Letrozol/uso terapêutico , Terapia Neoadjuvante , Hormônios/uso terapêutico , Microambiente Tumoral
15.
Curr Oncol ; 31(1): 50-65, 2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-38275830

RESUMO

Background: Brachytherapy (BT) is a critical component of radiotherapy for locally advanced cervical cancer (LACC), and it has rapidly developed in recent decades. Since the advent of three-dimensional image-guided adaptive brachytherapy (3D-IGABT), magnetic resonance imaging (MRI) has emerged as the primary modality for image guidance. Meanwhile, other imaging modalities, such as computed tomography, 18F-fluorodeoxyglucose positron emission tomography, ultrasound, and their combinations have also been widely studied. Materials and methods: We reviewed studies on different imaging modalities utilized for target delineation and planning. Emerging techniques in IGABT like real-time image guidance and 3D printing were also included. We summarized research on their feasibility and concentrated on their clinical outcomes. Results: MRI-guided BT was the gold standard, and CT-guided BT was the most widely applied. Other modalities have shown feasibility and promising efficacy in dosimetry studies and preliminary outcomes. The longer-term clinical outcomes associated with these approaches require further elucidation. Conclusions: As 3D-IGABT was validated by promising clinical outcomes, the future of BT for LACC is expected to progress toward the refinement of more effective image-guided procedures. Moreover, achieving operational consensus and driving technological advancements to mitigate the inherent limitations associated with different imaging modes remain essential.


Assuntos
Braquiterapia , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/patologia , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos
16.
Sci Rep ; 12(1): 22650, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-36587111

RESUMO

Adjuvant endocrine therapy improves the prognosis of early breast cancer with hormone receptor positivity. However, there is no systematic report on the effect of endocrine therapy (particularly ovarian function suppression, OFS) on serum lipids in premenopausal women. This retrospective cohort study aimed to determine whether various endocrine treatments had different effects on blood lipids. This study enrolled 160 premenopausal patients with stage I-III breast cancer in eastern China. The initial diagnostic information was retrieved from patient's medical records, including age at the time of diagnosis, tumor characteristics, anticancer treatment and past medical history. The changes in blood lipids in patients receiving different types of endocrine therapy were compared at the 3rd, 6th, 12th, and 24th months after initiating endocrine therapy. Generalized linear mixed model was used in our analyses. Our data revealed that low-density lipoprotein cholesterol (LDL-C) levels in patients with tamoxifen (TAM) were significantly lower in the 6th, 12th, and 24th months than that in the 3rd month, while high-density lipoprotein cholesterol (HDL-C) levels in the 6th, 12th, and 24th months were significantly higher than that in the 3rd month, indicating that blood lipid levels generally improved with time. While in TAM plus OFS group, HDL-C levels were significantly higher in the 24th month than in the 3rd month, total cholesterol (TC) levels were significantly higher in the 24th month than in the 6th month. The lipid profiles of OFS plus aromatase inhibitor (AI) group did not show significant differences at any time point but were significantly higher than those of the other two groups especially in LDL and TC. TAM group tended to have lower serum lipid levels. With longer follow-up, no statistically significant difference in values was observed between TAM and TAM plus OFS groups at various time points. Compared with the other two groups, OFS plus AI group presented an increasing trend toward LDL-C and TC. The risk of dyslipidemia requires further investigation using a large sample size.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/patologia , Antineoplásicos Hormonais/uso terapêutico , Estudos Retrospectivos , LDL-Colesterol , Quimioterapia Adjuvante , Tamoxifeno/uso terapêutico , Pré-Menopausa
17.
Support Care Cancer ; 31(1): 34, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36517615

RESUMO

PURPOSE: This systematic review and meta-analysis aimed to synthesize the evidence on the effect of couple-based interventions on quality of life (QOL) among prostate cancer patients and their spouses. METHOD: Six English databases and two Chinese databases were systematically searched to identify relevant RCTs that examined the effect of couple-based interventions on QOL. The data from the included studies were extracted by two independent reviewers using a standardized data extraction form. Methodological quality was assessed by using the Cochrane Risk of Bias Tool. Meta-analysis was conducted among the suitable studies that the available data were sufficient. RESULTS: One thousand ninety-five studies were identified, and 11 studies met the inclusion criteria for qualitative synthesis and 7 studied for meta-analysis. Couple-based interventions involve different formats of physical and psychosocial interventions. Physical exercise-based interventions were popular among couples, and these interventions had the highest level of adherence among all interventions examined herein. However, the meta-analysis of total QOL and physical and mental health revealed a non-significant effect on both prostate cancer patients and their spouses. More RCTs examining couple-based interventions may be needed in developing countries, especially in Asian countries. CONCLUSION: Couple-based interventions had non-significant effect on improving the total QOL and physical and mental health of prostate cancer patients and their spouses. However, the current evidence is limited because the sample size of the studies is small. Thus, more studies with large sample sizes need to be included to detect the efficacy of couple-based interventions on prostate cancer patients and their spouses.


Assuntos
Neoplasias da Próstata , Qualidade de Vida , Masculino , Humanos , Cônjuges/psicologia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/psicologia , Saúde Mental , Pacientes
18.
Front Immunol ; 13: 1007461, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36524115

RESUMO

Gliomas, originating from the glial cells, are the most lethal type of primary tumors in the central nervous system. Standard treatments like surgery have not significantly improved the prognosis of glioblastoma patients. Recently, immune therapy has become a novel and effective option. As a conserved group of transcriptional regulators, the Sry-type HMG box (SOX) family has been proved to have a correlation with numerous diseases. Based on the large-scale machine learning, we found that the SOX family, with significant immune characteristics and genomic profiles, can be divided into two distinct clusters in gliomas, among which SOX10 was identified as an excellent immune regulator of macrophage in gliomas. The high expression of SOX10 is related to a shorter OS in LGG, HGG, and pan-cancer groups but benefited from the immunotherapy. It turned out in single-cell sequencing that SOX10 is high in neurons, M1 macrophages, and neural stem cells. Also, macrophages are found to be elevated in the SOX10 high-expression group. SOX10 has a positive correlation with macrophage cytokine production and negative regulation of macrophages' chemotaxis and migration. In conclusion, our study demonstrates the outstanding cluster ability of the SOX family, indicating that SOX10 is an immune regulator of macrophage in gliomas, which can be an effective target for glioma immunotherapy.


Assuntos
Glioblastoma , Glioma , Macrófagos , Fatores de Transcrição SOXE , Humanos , Glioblastoma/patologia , Glioma/imunologia , Glioma/patologia , Aprendizado de Máquina , Macrófagos/imunologia , Macrófagos/metabolismo , Fatores de Transcrição SOXE/imunologia , Fatores de Transcrição SOXE/metabolismo
19.
Int J Mol Sci ; 23(22)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36430365

RESUMO

Alzheimer's disease (AD) is an incurable degenerative disease of the central nervous system and the most common type of dementia in the elderly. Despite years of extensive research efforts, our understanding of the etiology and pathogenesis of AD is still highly limited. Nevertheless, several hypotheses related to risk factors for AD have been proposed. Moreover, plant-derived dietary polyphenols were also shown to exert protective effects against neurodegenerative diseases such as AD. In this review, we summarize the regulatory effects of the most well-known plant-derived dietary polyphenols on several AD-related molecular mechanisms, such as amelioration of oxidative stress injury, inhibition of aberrant glial cell activation to alleviate neuroinflammation, inhibition of the generation and promotion of the clearance of toxic amyloid-ß (Aß) plaques, inhibition of cholinesterase enzyme activity, and increase in acetylcholine levels in the brain. We also discuss the issue of bioavailability and the potential for improvement in this regard. This review is expected to encourage further research on the role of natural dietary plant polyphenols in the treatment of AD.


Assuntos
Doença de Alzheimer , Produtos Biológicos , Humanos , Idoso , Doença de Alzheimer/patologia , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Peptídeos beta-Amiloides , Placa Amiloide/complicações
20.
Sci Rep ; 12(1): 18440, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36323863

RESUMO

In breast conserving surgery (BCS), specimen mammography is one of the most widely used intraoperative methods of assessing margin status. We performed a meta-analysis to evaluate the diagnostic accuracy of specimen mammography. Literature databases including PubMed, Cochrane Library, Web of Science, and EMBASE were searched prior to Jun 2022. A total of 1967 patients were included from 20 studies. A pooled analysis, heterogeneity testing, threshold effect testing, publication bias analysis, and subgroup analyses were performed from extracted data. The pooled weighted values were a sensitivity of 0.55 (95% confidence interval [CI], 0.47-0.63), a specificity of 0.85 (95% CI, 0.78-0.90), a diagnostic odds ratio of 7 (95% CI, 4-12), and a pooled positive likelihood ratio of 3.7 (95% CI 2.6-5.5). The area under the receiver operator characteristic curve was 0.75 (95% CI 0.71-0.78). In the subgroup analysis, the pooled specificity in the positive margin defined as tumor at margin subgroup was lower than the other positive margin definition subgroup (0.82 [95% CI: 0.71, 0.92] vs. 0.87 [95% CI: 0.80, 0.94], p = 0.01). Our findings indicated that specimen mammography was an accurate intraoperative imaging technique for margin assessment in BCS.


Assuntos
Neoplasias da Mama , Neoplasias , Humanos , Feminino , Mastectomia Segmentar , Mamografia , Margens de Excisão , Sensibilidade e Especificidade , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia
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