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1.
Gland Surg ; 11(5): 805-817, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35694096

RESUMO

Background: Trastuzumab has significantly improved the outcomes of human epidermal growth factor receptor 2 (HER2)-positive breast cancer over 20 years, and remains a cornerstone of treatment for this subtype today. Higher mortality was reported in underinsured breast cancer, but the mechanism remains unclear. Financial support for trastuzumab has transitioned from no support, to the Breast Cancer Assistant Program (BCAP), and finally, health insurance. Exploring the association between survival outcomes and different financial supports is necessary to further improve the outcomes of HER2-positive breast cancer in resource-limited regions. Methods: A prospective cohort of primary early unilateral HER2-positive breast cancer patients registered between January 2002 and December 2020 was used. Patients were divided into the following 3 groups, based on when they were diagnosed with breast cancer: (I) before 2011 (no financial support); (II) 2011-2017 (BCAP support); and (III) 2018 onwards (health insurance support). Overall survival and invasive disease-free survival (iDFS) were the primary outcomes. The follow-up was performed according the standard procedure. Cox proportional hazards regression was used to explore the association between financial support and prognosis with adjustment of demographic and clinicopathological characteristics, and treatments. Results: A total of 2,972 patients were finally identified. During the median follow-up period of 3.9 years, there were 153 breast cancer-related deaths. When fully adjusted potential covariates, patients supported by the BCAP had a 37% [hazard ratio (HR): 0.63, 95% CI: 0.41-0.96] decreased risk of overall mortality and that of patients covered by health insurance had a 64% decreased of overall mortality (HR: 0.36, 95% CI: 0.17-0.74) when compared with those who did not receive any financial support. Lower overall mortality was observed in patients covered by a higher reimbursement rate (HR: 0.68, 95% CI: 0.49-0.94) or the urban scheme (HR: 0.61, 95% CI: 0.43-0.86) than those covered by a lower reimbursement rate or the rural scheme. The same trends were also observed for iDFS and breast cancer-specific survival. Conclusions: Our findings revealed the independent role of financial support in improving the survival outcomes of the HER2-positive breast cancer in resource-limited regions and the underneath mechanism.

2.
Appl Environ Microbiol ; : e0048422, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35695571

RESUMO

Pit mud microbial consortia play crucial roles in the formation of Chinese strong-flavor baijiu's key flavor-active compounds, especially butyric and caproic acids. Clostridia, one of the abundant bacterial groups in pit mud, were recognized as important butyric and caproic acid producers. Research on the interactions of the pit mud microbial community mainly depends on correlation analysis at present. Interaction between Clostridium and other microorganisms and its involvement in short/medium-chain fatty acid (S/MCFA) metabolism are still unclear. We previously found coculture of two clostridial strains isolated from pit mud, Clostridium fermenticellae JN500901 (C.901) and Novisyntrophococcus fermenticellae JN500902 (N.902), could enhance S/MCFA accumulation. Here, we investigated their underlying interaction mechanism through the combined analysis of phenotype, genome, and transcriptome. Compared to monocultures, coculture of C.901 and N.902 obviously promoted their growth, including shortening the growth lag phase and increasing biomass, and the accumulation of butyric acid and caproic acid. The slight effects of inoculation ratio and continuous passage on the growth and metabolism of coculture indicated the relative stability of their interaction. Transwell coculture and transcriptome analysis showed the interaction between C.901 and N.902 was accomplished by metabolite exchange, i.e., formic acid produced by C.901 activated the Wood-Ljungdahl pathway of N.902, thereby enhancing its production of acetic acid, which was further converted to butyric acid and caproic acid by C.901 through reverse ß-oxidation. This work demonstrates the potential roles of mutually beneficial interspecies interactions in the accumulation of key flavor compounds in pit mud. IMPORTANCE Microbial interactions played crucial roles in influencing the assembly, stability, and function of the microbial community. The metabolites of pit mud microbiota are the key to flavor formation of Chinese strong-flavor baijiu. So far, researches on the interactions of the pit mud microbial community have been mainly based on the correlation analysis of sequencing data, and more work needs to be performed to unveil the complicated interaction patterns. Here, we identified a material exchange-based mutualistic interaction system involving two fatty acid-producing clostridial strains (Clostridium fermenticellae JN500901 and Novisyntrophococcus fermenticellae JN500902) isolated from pit mud and systematically elucidated their interaction mechanism for promoting the production of butyric acid and caproic acid, the key flavor-active compounds of baijiu. Our findings provide a new perspective for understanding the complicated interactions of pit mud microorganisms.

3.
Nat Commun ; 13(1): 3208, 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35680915

RESUMO

Malaria parasites are less vulnerable to mosquito immune responses once ookinetes transform into oocysts, facilitating parasite development in the mosquito. However, the underlying mechanisms of oocyst resistance to mosquito defenses remain unclear. Here, we show that circumsporozoite protein (CSP) is required for rodent malaria oocysts to avoid mosquito defenses. Mosquito infection with CSPmut parasites (mutation in the CSP pexel I/II domains) induces nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 5 (NOX5)-mediated hemocyte nitration, thus activating Toll pathway and melanization of mature oocysts, upregulating hemocyte TEP1 expression, and causing defects in the release of sporozoites from oocysts. The pre-infection of mosquitoes with the CSPmut parasites reduces the burden of infection when re-challenged with CSPwt parasites by inducing hemocyte nitration. Thus, we demonstrate why oocysts are invisible to mosquito immunity and reveal an unknown role of CSP in the immune evasion of oocysts, indicating it as a potential target to block malaria transmission.


Assuntos
Culicidae , Malária , Animais , Culicidae/parasitologia , Malária/parasitologia , Oocistos , Proteínas de Protozoários/metabolismo , Esporozoítos/fisiologia
4.
Food Res Int ; 156: 111298, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35651059

RESUMO

High-temperature Daqu, usually used as a fermentation starter for sauce-flavor Baijiu production, plays an essential role in the yield and flavor quality of Baijiu. The environmental heterogeneity of different locations in the workshop during fermentation led to the final production of Daqu with three different types (i.e., white, yellow, and black Daqu). How to use these three types of Daqu in Baijiu production mainly depends on the workers' experience so far. Here, we aimed to reveal the potential functions of different types of Daqu by comparing enzyme activity, volatile metabolites, and microbiota characteristics. White_Qu exhibited the highest liquefaction and saccharification enzyme activities, while the highest neutral proteinase and cellulase enzyme activities were detected in black_Qu. The total volatile content of yellow_Qu and black_Qu was roughly double that of white_Qu, and multivariate analysis revealed distinct volatile dissimilarities across different types of Daqu. Significant differences in bacterial and fungal community structures, assembly patterns, and potential functional profiles were discovered among different types of Daqu. At the genus level, Oceanobacillus and Thermomyces dominated the white_Qu microbiota, and the abundant microbes in yellow_Qu and black_Qu were scattered in Kroppenstedtia and Thermoascus. Bacterial and fungal communities were dominated by deterministic and stochastic assembly processes, respectively, suggesting that bacteria may be more affected by abiotic environmental factors and species interaction than fungi. Co-occurrence network analysis showed positive correlations characterized Daqu microbial networks, and network topological features indicated stronger interactions between bacterial taxa compared with fungal community. The Spearman correlation analysis revealed that four bacterial genera (Kroppenstedtia, Virgibacillus, Scopulibacillus, and Staphylococcus) and two fungal genera (Thermoascus and Aspergillus) exhibited positive correlations with almost all of the abundant volatiles. This work reveals that spatially varying environments lead to the microbiome and metabolome heterogeneity of high-temperature Daqu in the same workshop.


Assuntos
Microbiota , Bactérias , Fermentação , Humanos , Metaboloma , Temperatura
6.
BMC Cancer ; 22(1): 680, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729536

RESUMO

BACKGROUND: Experimental studies indicate that neuroendocrine pathways might play a role in progression of breast cancer. We aim to test the hypothesis that somatic mutations in the genes of neuroendocrine pathways influence breast cancer prognosis, through dysregulated gene expression in tumor tissue. METHODS: We conducted an extreme case-control study including 208 breast cancer patients with poor invasive disease-free survival (iDFS) and 208 patients with favorable iDFS who were individually matched on molecular subtype from the Breast Cancer Cohort at West China Hospital (WCH; N = 192) and The Cancer Genome Atlas (TCGA; N = 224). Whole exome sequencing and RNA sequencing of tumor and paired normal breast tissues were performed. Adrenergic, glucocorticoid, dopaminergic, serotonergic, and cholinergic pathways were assessed for differences in mutation burden and gene expression in relation to breast cancer iDFS using the logistic regression and global test, respectively. RESULTS: In the pooled analysis, presence of any somatic mutation (odds ratio = 1.66, 95% CI: 1.07-2.58) of the glucocorticoid pathway was associated with poor iDFS and a two-fold increase of tumor mutation burden was associated with 17% elevated odds (95% CI: 2-35%), after adjustment for cohort membership, age, menopausal status, molecular subtype, and tumor stage. Differential expression of genes in the glucocorticoid pathway in tumor tissue (P = 0.028), but not normal tissue (P = 0.701), was associated with poor iDFS. Somatic mutation of the adrenergic and cholinergic pathways was significantly associated with iDFS in WCH, but not in TCGA. CONCLUSION: Glucocorticoid pathway may play a role in breast cancer prognosis through differential mutations and expression. Further characterization of its functional role may open new avenues for the development of novel therapeutic targets for breast cancer.

7.
J Transl Med ; 20(1): 275, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35715864

RESUMO

BACKGROUND: Prostate cancer (PCa) is the second most prevalent cancer in males worldwide, yet detecting PCa and its metastases remains a major challenging task in clinical research setups. The present study aimed to characterize the metabolic changes underlying the PCa progression and investigate the efficacy of related metabolic panels for an accurate PCa assessment. METHODS: In the present study, 75 PCa subjects, 62 PCa patients with bone metastasis (PCaB), and 50 benign prostatic hyperplasia (BPH) patients were enrolled, and we performed a cross-sectional metabolomics analysis of serum samples collected from these subjects using a 1H nuclear magnetic resonance (NMR)-based metabolomics approach. RESULTS: Multivariate analysis revealed that BPH, PCa, and PCaB groups showed distinct metabolic divisions, while univariate statistics integrated with variable importance in the projection (VIP) scores identified a differential metabolite series, which included energy, amino acid, and ketone body metabolism. Herein, we identified a series of characteristic serum metabolic changes, including decreased trends of 3-HB and acetone as well as elevated trends of alanine in PCa patients compared with BPH subjects, while increased levels of 3-HB and acetone as well as decreased levels of alanine in PCaB patients compared with PCa. Additionally, our results also revealed the metabolic panels of discriminant metabolites coupled with the clinical parameters (age and body mass index) for discrimination between PCa and BPH, PCaB and BPH, PCaB and PCa achieved the AUC values of 0.828, 0.917, and 0.872, respectively. CONCLUSIONS: Overall, our study gave successful discrimination of BPH, PCa and PCaB, and we characterized the potential metabolic alterations involved in the PCa progression and its metastases, including 3-HB, acetone and alanine. The defined biomarker panels could be employed to aid in the diagnosis and classification of PCa in clinical practice.


Assuntos
Hiperplasia Prostática , Neoplasias da Próstata , Acetona , Alanina , Estudos Transversais , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Metabolômica/métodos , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/patologia , Espectroscopia de Prótons por Ressonância Magnética
8.
Pediatr Infect Dis J ; 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35703281

RESUMO

A 9-year-old girl with remarkable hyponatremia was diagnosed with SIADH that was likely secondary to varicella. Under appropriate treatment, her serum sodium returned to the normal level. There was no evidence of hyponatremia at a 3-month follow-up. We propose that medical professionals need to consider the existence of that SIADH when treating patients with varicella who present with severe hyponatremia.

9.
Leukemia ; 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35697791

RESUMO

Loss-of-function TET2 mutations are recurrent somatic lesions in chronic myelomonocytic leukemia (CMML). KDM6B encodes a histone demethylase involved in innate immune regulation that is overexpressed in CMML. We conducted genomic and transcriptomic analyses in treatment naïve CMML patients and observed that the patients carrying both TET2 mutations and KDM6B overexpression constituted 18% of the cohort and 42% of patients with TET2 mutations. We therefore hypothesized that KDM6B overexpression cooperated with TET2 deficiency in CMML pathogenesis. We developed a double-lesion mouse model with both aberrations, and discovered that the mice exhibited a more prominent CMML-like phenotype than mice with either Tet2 deficiency or KDM6B overexpression alone. The phenotype includes monocytosis, anemia, splenomegaly, and increased frequencies and repopulating activity of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs). Significant transcriptional alterations were identified in double-lesion mice, which were associated with activation of proinflammatory signals and repression of signals maintaining genome stability. Finally, KDM6B inhibitor reduced BM repopulating activity of double-lesion mice and tumor burden in mice transplanted with BM-HSPCs from CMML patients with TET2 mutations. These data indicate that TET2 deficiency and KDM6B overexpression cooperate in CMML pathogenesis of and that KDM6B could serve as a potential therapeutic target in this disease.

10.
Nat Med ; 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710987

RESUMO

Timely evaluation of the protective effects of Coronavirus Disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern is urgently needed to inform pandemic control planning. Based on 78 vaccine efficacy or effectiveness (VE) data from 49 studies and 1,984,241 SARS-CoV-2 sequences collected from 31 regions, we analyzed the relationship between genetic distance (GD) of circulating viruses against the vaccine strain and VE against symptomatic infection. We found that the GD of the receptor-binding domain of the SARS-CoV-2 spike protein is highly predictive of vaccine protection and accounted for 86.3% (P = 0.038) of the VE change in a vaccine platform-based mixed-effects model and 87.9% (P = 0.006) in a manufacturer-based model. We applied the VE-GD model to predict protection mediated by existing vaccines against new genetic variants and validated the results by published real-world and clinical trial data, finding high concordance of predicted VE with observed VE. We estimated the VE against the Delta variant to be 82.8% (95% prediction interval: 68.7-96.0) using the mRNA vaccine platform, closely matching the reported VE of 83.0% from an observational study. Among the four sublineages of Omicron, the predicted VE varied between 11.9% and 33.3%, with the highest VE predicted against BA.1 and the lowest against BA.2, using the mRNA vaccine platform. The VE-GD framework enables predictions of vaccine protection in real time and offers a rapid evaluation method against novel variants that may inform vaccine deployment and public health responses.

11.
Arch Virol ; 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35716263

RESUMO

A novel positive-sense single-stranded RNA mycovirus, designated as "Magnaporthe oryzae botourmiavirus 10" (MoBV10), was identified in the rice blast fungus Magnaporthe oryzae isolate HF04. MoBV10 has a single genomic RNA segment consisting of 2,448 nucleotides, which contains a single open reading frame encoding an RNA-dependent RNA polymerase. Genome comparison and phylogenetic analysis indicated that MoBV10 is a new member of the genus Betascleroulivirus in the family Botourmiaviridae. The 5'- and 3'-terminal sequences of the genomic RNA of MoBV10 have inverted complementarity and potentially form a panhandle structure, which is very rare in RNA viruses.

12.
Nat Commun ; 13(1): 2448, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508497

RESUMO

The ecological and oceanographic processes that drive the response of pelagic ocean microbiomes to environmental changes remain poorly understood, particularly in coastal upwelling ecosystems. Here we show that seasonal and interannual variability in coastal upwelling predicts pelagic ocean microbiome diversity and community structure in the Southern California Current region. Ribosomal RNA gene sequencing, targeting prokaryotic and eukaryotic microbes, from samples collected seasonally during 2014-2020 indicate that nitracline depth is the most robust predictor of spatial microbial community structure and biodiversity in this region. Striking ecological changes occurred due to the transition from a warm anomaly during 2014-2016, characterized by intense stratification, to cooler conditions in 2017-2018, representative of more typical upwelling conditions, with photosynthetic eukaryotes, especially diatoms, changing most strongly. The regional slope of nitracline depth exerts strong control on the relative proportion of highly diverse offshore communities and low biodiversity, but highly productive nearshore communities.


Assuntos
Microbiota , Plâncton , Biodiversidade , Ecossistema , Microbiota/genética , Nutrientes , Plâncton/genética , Água do Mar
14.
Nanoscale ; 14(21): 7856-7863, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35583119

RESUMO

Multidrug resistance (MDR) has become one of the most intractable problems in clinics as it would cause failure in chemotherapy. In this study, we demonstrated that a nanoscale self-assembled nanomedicine, which almost consisted of a pure chemo-drug, could efficiently overcome MDR. Celastrol (CST) was directly assembled into a discrete nanomedicine by precipitation, and then CST nanoparticles (CNPs) inhibited drug efflux pumps by activating HSF-1 expression and promoting HSF-1 translocation into nucleus to suppress the Pgp expression. The more drug accumulated in cells could activate apoptosis signals simultaneously and realize drug resistance reversal. CNPs significantly increased the level of ROS to regulate ERK/JNK signaling, which would further induce resistant cell apoptosis. The tandem apoptosis strategy used the same concentration of CST but achieved a higher antitumor effect. Overall, our study provides a new translational and alternative strategy using conventional natural products to overcome MDR with high efficacy.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Neoplasias/tratamento farmacológico , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/uso terapêutico
15.
Org Biomol Chem ; 20(23): 4782-4786, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35635197

RESUMO

A novel near-infrared fluorescent probe (SWJT-2) has been designed and synthesized for the detection of methylglyoxal (MGO). It showed a low detection limit (0.32 µM), high selectivity and the fastest detection (15 min) over various reactive carbonyl compounds in aqueous solution. SWJT-2 had been successfully applied to bioimaging in HeLa cells to detect exogenous and endogenous MGO.


Assuntos
Corantes Fluorescentes , Aldeído Pirúvico , Células HeLa , Humanos , Óxido de Magnésio , Imagem Óptica/métodos
16.
J Oncol Pharm Pract ; : 10781552221102311, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35593090

RESUMO

INTRODUCTION: We present a case of Trousseau's syndrome in a non-small cell lung cancer patient recurrently aggravated by pembrolizumab. The adverse events related to immune checkpoint inhibitors (ICIs) on thrombogenesis remain unclear. CASE REPORT: A 48-year-old woman was diagnosed with right lung adenocarcinoma (cT1bN3M1a, IVA) and with programmed cell death-1 positive. Brain magnetic resonance imaging (MRI) showed multiple asymptomatic bilateral cerebral infarctions as Trousseau's syndrome. After the patient was administered pembrolizumab, bilateral cerebral infarctions were aggravated. MANAGEMENT AND OUTCOME: Although the patient was given prophylactic anticoagulant therapy respectively before two doses of pembrolizumab, Trousseau's syndrome still aggravated recurrently. DISCUSSION: Trousseau's syndrome is rarely reported following the administration of ICIs. It is possible that pembrolizumab may trigger disorders of the coagulation-fibrinolysis system in cancer patients.

17.
J Multidiscip Healthc ; 15: 907-920, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35519154

RESUMO

Progress in medical and surgical care has tremendously improved the survival rates of children with congenital heart disease (CHD). However, reduced aerobic capacity and health-related issues remain a threaten to quality survival and prevention of related complications among children and adolescents with CHD. This research program aims to develop and evaluate a WeChat-based health platform (HeartFIT) to facilitate cardiac rehabilitation and promote physical fitness for this rapidly expanding young population. The study protocol describes the use of an iterative process of using a mixed-methods strategy to develop, refine, and pilot test the proposed HeartFIT platform. A sequential problem-solving process comprising four iterative phases with ongoing end-user input will be implemented. In phase 1, relevant literature was systematically reviewed (completed) and then child-parent dyads will be interviewed to understand the broad context and the requirements and considerations of the target population toward the WeChat-based rehabilitation platform. In phase 2, key features and priority functionalities for the platform will be ideated and refined, and a digital interactive prototype will be created. In phase 3, heuristic evaluation and three rounds of end-user testing will be conducted to ensure further refinement and usability of the prototype. In phase 4, a prospective pilot study will be performed to investigate the feasibility, acceptability, and preliminary efficacy of the developed platform over a 12-week intervention period. If HeartFIT intervention is feasible, acceptable, and demonstrates promising efficacy, an adequately powered randomized controlled trial (future work) will be deployed to test the real-world effectiveness of the intervention.

18.
Transl Lung Cancer Res ; 11(4): 523-542, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35529784

RESUMO

Background: Macrophages are critical players in regulating innate and adaptive immunity in the tumor microenvironment (TME). The prognostic value of macrophages and their heterogeneous phenotypes in non-small cell lung cancer (NSCLC) is still uncertain. Methods: Surgically-resected samples of 681 NSCLC cases were stained by multiplex immunofluorescence to examine macrophage phenotypes as well as the expression levels of program death-ligand 1 (PD-L1) on them in both tumor nest and tumor stroma, including pan-macrophage (CD68+), M1 (CD68+CD163-), and M2 macrophages (CD68+CD163+). Various other immune cell markers, including CD4, CD8, CD20, CD38, CD66B, FOXP3, and CD133, were also evaluated. Machine learning algorithm by Random Forest (RF) model was utilized to screen the robust prognostic markers and construct the CD68-based immune-related risk score (IRRS) for predicting disease-free survival (DFS). Results: The expression levels of CD68 were moderately correlated with the levels of PD-L1 (P<0.001), CD133 (P<0.001), and CD8 (P<0.001). Higher levels of CD68 (OR 1.03, 95% CI: 1.01-1.05, P<0.001) as well as M1 macrophage (OR 1.04, 95% CI: 1.01-1.06, P<0.001) indicated shorter DFS. Despite without statiscial significance, intratumoral M2 macrophage (OR 1.05, 95% CI: 0.99-1.10, P=0.081) was also associated with worse DFS. IRRS incorporating three intratumoral CD68-related markers and four intrastromal markers was constructed and validated to predict recurrence (high-risk group vs. low-risk group: OR 2.52, 95% CI: 1.89-3.38, P<0.001). The IRRS model showed good accuracy [area under the curve (AUC) =0.670, 0.709, 0.695, 0.718 for 1-, 3-, 5-year, and overall DFS survival, respectively] and the predictive performance was better than the single-marker model (area under the curve 0.718 vs. 0.500-0.654). A nomogram based on clinical characteristics and IRRS for relapse prediction was then established and exhibited better performance than the tumor-node-metastasis (TNM) classification and IRRS system (C-index 0.76 vs. 0.69 vs. 0.60, 0.74 vs. 0.67 vs. 0.60, 0.81 vs. 0.74 vs. 0.60 of the entire, training, testing cohort, respectively). Conclusions: Our study suggested close interactions between CD68 and other immune markers in TME, demonstrating the prognostic value of CD68 in relapse prediction in resectable NSCLC.

19.
Front Immunol ; 13: 868813, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35514975

RESUMO

Breast cancer development and progression rely not only on the proliferation of neoplastic cells but also on the significant heterogeneity in the surrounding tumor microenvironment. Its unique microenvironment, including tumor-infiltrating lymphocytes, complex myeloid cells, lipid-associated macrophages, cancer-associated fibroblasts (CAFs), and other molecules that promote the growth and migration of tumor cells, has been shown to play a crucial role in the occurrence, growth, and metastasis of breast cancer. However, a detailed understanding of the complex microenvironment in breast cancer remains largely unknown. The unique pattern of breast cancer microenvironment cells has been poorly studied, and neither has the supportive role of these cells in pathogenesis been assessed. Single-cell multiomics biotechnology, especially single-cell RNA sequencing (scRNA-seq) reveals single-cell expression levels at much higher resolution, finely dissecting the molecular characteristics of tumor microenvironment. Here, we review the recent literature on breast cancer microenvironment, focusing on scRNA-seq studies and analyzing heterogeneity and spatial location of different cells, including T and B cells, macrophages/monocytes, neutrophils, and stromal cells. This review aims to provide a more comprehensive perception of breast cancer microenvironment and annotation for their clinical classification, diagnosis, and treatment. Furthermore, we discuss the impact of novel single-cell omics technologies, such as abundant omics exploration strategies, multiomics conjoint analysis mode, and deep learning network architecture, on the future research of breast cancer immune microenvironment.


Assuntos
Neoplasias da Mama , Fibroblastos Associados a Câncer , Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/metabolismo , Feminino , Humanos , Linfócitos do Interstício Tumoral , Análise de Célula Única , Microambiente Tumoral
20.
Front Oncol ; 12: 889862, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574312

RESUMO

Objective: Cervical cancer is a common gynecological malignancy. In addition to the open radical hysterectomy (ORH) and laparoscopic radical hysterectomy (LRH), laparoscopic nerve-sparing radical hysterectomy (LNSRH) could be another treatment option since it could preserve urinary, colorectal, and sexual functions. However, LNSRH might result in early cancer metastasis and recurrence due to inadequate tumor resection. Additionally, whether LNSRH should be considered based on perineural invasion (PNI) status remains controversial. To assess different types of hysterectomy on the outcome of early cervical cancer with PIN. Methods: A retrospective study was performed in early cervical cancer patients who received ORH, LRH, or LNSRH between January 2012 and December 2019. Age, FIGO cancer stages, histopathological types, tumor size, histological grade, invasion depth, lymph node metastasis, lymphovascular space invasion, and PNI were documented. Disease-free survival (DFS) and overall survival (OS) were recorded. Results: A total of 174 patients were included, with 33, 69, and 72 patients received LRH, ORH, and LNSRH, respectively. Twenty-one patients (12.1%) had PNI. DFS (P = 0.000) and OS (P = 0.022) periods were shortened in positive PNI patients than in negative PNI patients (P = 0.000 and 0.022, respectively). In patients with positive PNI, lymph node metastasis, but not the surgery type, was an independent risk factor for DFS and OS (P = 0.000). Conclusion: Early cervical cancer patients with PNI had shorter postoperative DFS and OS periods. In these patients, lymph node metastasis, but not the type of hysterectomy, was independently associated with DFS and OS.

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