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1.
Int Immunopharmacol ; 131: 111878, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38493693

RESUMO

BACKGROUND: Kidney renal papillary cell carcinoma (KIRP) is frequently associated with an unfavorable prognosis for affected individuals. Unfortunately, there has been insufficient exploration in search for a reliable prognosis signature and predictive indicators to forecast outcomes for KIRP patients. AIM: The aim of this study is to employ a comprehensive analysis of data for the identification of prognosis genes, leading to the development of a nomogram with strong predictive capabilities. The objective is to provide a valuable statistical tool that, when implemented in a clinical setting, can offer patients an early opportunity for treatment and enhance their chances of ultimate recovery from this life-threatening disease. METHODS: Different packages in R were used to analyze RNA-seq data from the TCGA data portal. Multivariate Cox regression analysis and Kaplan-Meier analysis were also used to investigate the prognostic values of immune-related genes and construct the predictive model and nomogram. A p-value < 0.05 was considered to be significant. RESULTS: A total of 368 immune-related genes and 60 TFs were identified as differentially expressed in KIRP tissues compared with normal tissues. Of the 368, 23 were found to be related to overall survival. GO and KEGG analysis suggested that these prognostic immune-related genes mainly participated in the ERK1 and ERK2 cascades, Rap1 signaling pathway, and the PI3K-Akt signaling pathway. 9 genes were identified from Cox regression to be statistically significant prognostic-related genes. Survival analysis showed that a model based on these 9 prognostic-related genes has high predictive performance. Immunohistochemistry results show that APOH, BIRC5, CCL19, and GRN were significantly increased in kidney cancer. B cells and CD4 + T cells were positively correlated with risk score model. CONCLUSION: A prognostic model was successfully created based on 9 immune-related genes correlated with overall survival in KIRP. This work aims to provide some insight into therapeutic approaches and prognostic predictors of KIRP.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Prognóstico , Nomogramas , Fosfatidilinositol 3-Quinases , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Rim
2.
Cancers (Basel) ; 16(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473313

RESUMO

Tumor cells gain advantages in growth and survival by acquiring genotypic and phenotypic heterogeneity. Interactions with bystander cells in the tumor microenvironment contribute to the progression of heterogeneity. We have shown that fusion between tumor and bystander cells is one form of interaction, and that tumor-bystander cell fusion has contrasting effects. By trapping fusion hybrids in the heterokaryon or synkaryon state, tumor-bystander cell fusion prevents the progression of heterogeneity. However, if trapping fails, fusion hybrids will resume replication to form derivative clones with diverse genomic makeups and behavioral phenotypes. To determine the characteristics of bystander cells that influence the fate of fusion hybrids, we co-cultured prostate mesenchymal stromal cell lines and their spontaneously transformed sublines with LNCaP as well as HPE-15 prostate cancer cells. Subclones derived from cancer-stromal fusion hybrids were examined for genotypic and phenotypic diversifications. Both stromal cell lines were capable of fusing with cancer cells, but only fusion hybrids with the transformed stromal subline generated large numbers of derivative subclones. Each subclone had distinct cell morphologies and growth behaviors and was detected with complete genomic hybridization. The health conditions of the bystander cell compartment play a crucial role in the progression of tumor cell heterogeneity.

3.
Front Oncol ; 14: 1371421, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38511141

RESUMO

Pancreatic cancer is one of the deadliest malignant tumors, which is a serious threat to human health and life, and it is expected that pancreatic cancer may be the second leading cause of cancer death in developed countries by 2030. Claudin18.2 is a tight junction protein expressed in normal gastric mucosal tissues, which is involved in the formation of tight junctions between cells and affects the permeability of paracellular cells. Claudin18.2 is highly expressed in pancreatic cancer and is associated with the initiation, progression, metastasis and prognosis of cancer, so it is considered a potential therapeutic target. Up to now, a number of clinical trials for Claudin18.2 are underway, including solid tumors such as pancreatic cancers and gastric cancers, and the results of these trials have not yet been officially announced. This manuscript briefly describes the Claudia protein, the dual roles of Cluadin18 in cancers, and summarizes the ongoing clinical trials targeting Claudin18.2 with a view to integrating the research progress of Claudin18.2 targeted therapy. In addition, this manuscript introduces the clinical research progress of Claudin18.2 positive pancreatic cancer, including monoclonal antibodies, bispecific antibodies, antibody-drug conjugates, CAR-T cell therapy, and hope to provide feasible ideas for the clinical treatment of Claudin18.2 positive pancreatic cancer.

4.
Transl Oncol ; 41: 101893, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38290250

RESUMO

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis. The number of cases increased by 2.26 million in 2020, making it the most commonly diagnosed cancer type in the world. TNBCs lack hormone receptor (HR) and human epidermal growth factor 2 (HER2), which limits treatment options. Currently, paclitaxel-based drugs combined with other chemotherapeutics remain the main treatment for TNBC. There is currently no consensus on the best therapeutic regimen for TNBC. However, there have been successful clinical trials exploring large-molecule monoclonal antibodies, small-molecule targeted drugs, and novel antibody-drug conjugate (ADC). Although monoclonal antibodies have produced clinical success, their large molecular weight can limit therapeutic benefits. It is worth noting that in the past 30 years, the FDA has approved small molecule drugs for HER2-positive breast cancers. The lack of effective targets and the occurrence of drug resistance pose significant challenges in the treatment of TNBC. To improve the prognosis of TNBC, it is crucial to search for effective targets and to overcome drug resistance. This review examines the clinical efficacy, adverse effects, resistance mechanisms, and potential solutions of targeted small molecule drugs in both monotherapies and combination therapies. New therapeutic targets, including nuclear export protein 1 (XPO1) and hedgehog (Hh), are emerging as potential options for researchers and become integrated into clinical trials for TNBC. Additionally, there is growing interest in the potential of targeted protein degradation chimeras (PROTACs), degraders of rogue proteins, as a future therapy direction. This review provides potentially valuable insights with clinical implications.

5.
Mol Pharm ; 21(2): 873-882, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38229228

RESUMO

Prostate cancer (PC), particularly its metastatic castration-resistant form (mCRPC), is a leading cause of cancer-related deaths among men in the Western world. Traditional systemic treatments, including hormonal therapy and chemotherapy, offer limited effectiveness due to tumors' inherent resistance to these therapies. Moreover, they often come with significant side effects. We have developed a delivery method using a tumor-cell-specific heptamethine carbocyanine dye (DZ) designed to transport therapeutic agents directly to tumor cells. This research evaluated simvastatin (SIM) as the antitumor payload because of its demonstrated chemopreventive effects on human cancers and its well-documented safety profile. We designed and synthesized a DZ-SIM conjugate for tumor cell targeting. PC cell lines and xenograft tumor models were used to assess tumor-cell targeting specificity and killing activity and to investigate the corresponding mechanisms. DZ-SIM treatment effectively killed PC cells regardless of their androgen receptor status or inherent therapeutic resistance. The conjugate targeted and suppressed xenograft tumor formation without harming normal cells of the host. In cancer cells, DZ-SIM was enriched in subcellular organelles, including mitochondria, where the conjugate formed adducts with multiple proteins and caused the loss of transmembrane potential, promoting cell death. The DZ-SIM specifically targets PC cells and their mitochondria, resulting in a loss of mitochondrial function and cell death. With a unique subcellular targeting strategy, the conjugate holds the potential to outperform existing chemotherapeutic drugs. It presents a novel strategy to circumvent therapeutic resistance, offering a more potent treatment for mCRPC.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Sinvastatina , Masculino , Humanos , Sinvastatina/farmacologia , Sinvastatina/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Próstata/metabolismo , Carbocianinas , Linhagem Celular Tumoral
6.
Eur J Gastroenterol Hepatol ; 36(1): 62-75, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37942763

RESUMO

BACKGROUND: The onset of colorectal adenomas (CRAs) is significantly associated with colorectal cancer. The preventive effects of chemical drugs on the recurrence of CRAs have been evaluated in a large number of randomized controlled trials (RCTs). However, there are still uncertainties about the relative effectiveness of such chemical drugs. METHODS: We searched relevant RCTs published in six databases up to February 2023. The quality of the included studies was assessed by using the Cochrane risk of bias assessment tool and Review Manager 5.4. Pairwise comparison and network meta-analysis (NMA) were conducted using RStudio to compare the effects of chemical drugs on the recurrence of CRAs. RESULTS: Forty-five high-quality RCTs were included. A total of 35 590 (test group: 20 822; control group: 14 768) subjects with a history of CRAs have been enrolled and randomized to receive placebo treatment or one of 24 interventions. Based on surface under the cumulative ranking values and NMA results, difluoromethylornithine (DFMO) + Sulindac significantly reduced the recurrence of CRAs, followed by berberine and nonsteroidal antiinflammatory drugs. CONCLUSION: DFMO + Sulindac is more effective in reducing the recurrence of CRAs but has a high risk of adverse events. Considering drug safety, tolerance, and compliance, berberine has a brighter prospect of clinical development. However, further studies are needed to verify our findings.


Assuntos
Adenoma , Berberina , Neoplasias Colorretais , Humanos , Sulindaco , Metanálise em Rede , Neoplasias Colorretais/prevenção & controle , Adenoma/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Int J Colorectal Dis ; 38(1): 246, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37787779

RESUMO

BACKGROUND: A watch-and-wait (WW) strategy or surgery for low to intermediate rectal cancer that has reached clinical complete remission (cCR) after neoadjuvant chemotherapy (nCRT) or total neoadjuvant therapy (TNT) has been widely used in the clinic, but both treatment strategies are controversial. OBJECTIVE: The aim of this study was to compare the oncologic outcomes of a watch-and-wait strategy or a surgical approach to treat rectal cancer in complete remission and to report the evidence-based clinical advantages of the two treatment strategies. METHODS: Seven national and international databases were searched for clinical trials comparing the watch-and-wait strategy with surgical treatment for oncological outcomes in patients with rectal cancer in clinical complete remission. RESULTS: In terms of oncological outcomes, there was no significant difference between the watch-and-wait strategy and surgical treatment in terms of overall survival (OS) (HR = 0.92, 95% CI (0.52, 1.64), P = 0.777), and subgroup analysis showed no significant difference in 5-year disease-free survival (5-year DFS) between WW and both local excision (LE) and radical surgery (RS) (HR = 1.76, 95% CI (0.97, 3.19), P = 0.279; HR = 1.98, 95% CI (0.95, 4.13), P = 0.164), in distant metastasis rate (RR = 1.12, 95% CI (0.73, 1.72), P = 0.593), mortality rate (RR = 1.62, 95% CI (0.93, 2.84), P = 0.09), and organ preservation rate (RR = 1.05, 95% CI (0.94, 1.17), P = 0.394) which were not statistically significant and on the outcome indicators of local recurrence rate (RR = 2.09, 95% CI (1.44, 3.03), P < 0.001) and stoma rate (RR = 0.35, 95% CI (0.20, 0.61), P < 0.001). There were significant differences between the WW group and the surgical treatment group. CONCLUSION: There were no differences in OS, 5-year DFS, distant metastasis, and mortality between the WW strategy group and the surgical treatment group. The WW strategy did not increase the risk of local recurrence compared with local resection but may be at greater risk of local recurrence compared with radical surgery, and the WW group was significantly better than the surgical group in terms of stoma rate; the WW strategy was evidently superior in preserving organ integrity compared to radical excision. Consequently, for patients who exhibit a profound inclination towards organ preservation and the evasion of stoma formation in the scenario of clinically complete remission of rectal cancer, the WW strategy can be contemplated as a pragmatic alternative to surgical interventions. It is, however, paramount to emphasize that the deployment of such a strategy should be meticulously undertaken within the ambit of a multidisciplinary team's management and within specialized centers dedicated to rectal cancer management.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Neoplasias Retais , Humanos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Indução de Remissão , Intervalo Livre de Doença , Quimiorradioterapia , Terapia Neoadjuvante , Conduta Expectante , Recidiva Local de Neoplasia/tratamento farmacológico , Resultado do Tratamento
8.
Discov Oncol ; 14(1): 179, 2023 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-37741920

RESUMO

Various new treatments are emerging constantly in anti-tumor therapies, including chemotherapy, immunotherapy, and targeted therapy. However, the efficacy is still not satisfactory. Astragalus polysaccharide is an important bioactive component derived from the dry root of Radix astragali. Studies found that astragalus polysaccharides have gained great significance in increasing the sensitivity of anti-tumor treatment, reducing the side effects of anti-tumor treatment, reversing the drug resistance of anti-tumor drugs, etc. In this review, we focused on the role of astragalus polysaccharides in tumor immune microenvironment. We reviewed the immunomodulatory effect of astragalus polysaccharides on macrophages, dendritic cells, natural killer cells, T lymphocytes, and B lymphocytes. We found that astragalus polysaccharides can promote the activities of macrophages, dendritic cells, natural killer cells, T lymphocytes, and B lymphocytes and induce the expression of a variety of cytokines and chemokines. Furthermore, we summarized the clinical applications of astragalus polysaccharides in patients with digestive tract tumors. We summarized the effective mechanism of astragalus polysaccharides on digestive tract tumors, including apoptosis induction, proliferation inhibition, immunoactivity regulation, enhancement of the anticancer effect and chemosensitivity. Therefore, in view of the multiple functions of astragalus polysaccharides in tumor immune microenvironment and its clinical efficacy, the combination of astragalus polysaccharides with antitumor therapy such as immunotherapy may provide new sparks to the bottleneck of current treatment methods.

9.
Eur J Gastroenterol Hepatol ; 35(10): 1075-1087, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37577790

RESUMO

This study aims to assess the risk of colorectal stricture progressing to colorectal neoplasia (CRN) in patients with inflammatory bowel disease (IBD). The literature from PubMed, Embase, Web of Science, and Cochrane Library databases was searched from the date of databases' creation to 5 November 2022. The Newcastle-Ottawa Scale was used to evaluate the quality of the included literature. Meta-analysis was conducted using the Stata 15 software and R 4.04 software. Two case-control studies and 12 cohort studies were eventually included. Colorectal stricture in patients with IBD increased the risk of progressing to CRN [odds ratio (OR): 1.52, 95% confidence interval (CI): 1.02-2.29, P = 0.042], but was irrelevant to the risk of progressing to ACRN (OR: 3.56, 95% CI 0.56-22.70, P = 0.180). The risk of CRN were further distinguished in patients with ulcerative colitis (UC) and Crohn's disease (CD) Our findings showed that colorectal stricture may increase the risk of progressing to CRN in patients with UC (OR = 3.53, 95%CI 1.62-7.68, P = 0.001), but was irrelevant to the risk of progressing to CRN in patients with CD (OR = 1.09, 95% CI 0.54-2.21, P = 0.811). In conclusion, colorectal stricture in patients with IBD can be used as a risk factor for predicting CRN but cannot be used as a risk factor for predicting ACRN. Stricture is a risk factor for CRN in patients with UC but not in patients with CD. More prospective, multi-center studies with large samples are expected to confirm our findings.


Assuntos
Colite Ulcerativa , Neoplasias Colorretais , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Constrição Patológica , Incidência , Estudos Prospectivos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/epidemiologia , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Fatores de Risco
10.
Front Oncol ; 13: 1197698, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37305582

RESUMO

Hepatocellular carcinoma is a common gastrointestinal malignancy with a high mortality rate and limited treatment options. Molecularly targeted drugs combined with immune checkpoint inhibitors have shown unique advantages over single-agent applications, significantly prolonging patient survival. This paper reviews the research progress of molecular-targeted drugs combined with immune checkpoint inhibitors in the treatment of hepatocellular carcinoma and discusses the effectiveness and safety of the combination of the two drugs to provide a reference for the further application of molecular-targeted drugs combined with immune checkpoint inhibitors in clinical practice.

11.
BMC Cancer ; 23(1): 499, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37268911

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and is notorious for its resistance to both chemotherapy and small-molecule inhibitor targeted therapies. Subcellular targeted cancer therapy may thwart the resistance to produce a substantial effect. METHODS: We tested whether the resistance can be circumvented by subcellular targeted cancer therapy with DZ-CIS, which is a chemical conjugate of the tumor-cell specific heptamethine carbocyanine dye (HMCD) with cisplatin (CIS), a chemotherapeutic drug with limited use in ccRCC treatment because of frequent renal toxicity. RESULTS: DZ-CIS displayed cytocidal effects on Caki-1, 786-O, ACHN, and SN12C human ccRCC cell lines and mouse Renca cells in a dose-dependent manner and inhibited ACHN and Renca tumor formation in experimental mouse models. Noticeably, in tumor-bearing mice, repeated DZ-CIS use did not cause renal toxicity, in contrast to the CIS-treated control animals. In ccRCC tumors, DZ-CIS treatment inhibited proliferation markers but induced cell death marker levels. In addition, DZ-CIS at half maximal inhibitory concentration (IC50) sensitized Caki-1 cells to small-molecule mTOR inhibitors. Mechanistically, DZ-CIS selectively accumulated in ccRCC cells' subcellular organelles, where it damages the structure and function of mitochondria, leading to cytochrome C release, caspase activation, and apoptotic cancer cell death. CONCLUSIONS: Results from this study strongly suggest DZ-CIS be tested as a safe and effective subcellular targeted cancer therapy.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Animais , Camundongos , Carcinoma de Células Renais/patologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Renais/patologia , Apoptose , Morte Celular , Linhagem Celular Tumoral , Proliferação de Células
12.
Int J Colorectal Dis ; 38(1): 132, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37193915

RESUMO

BACKGROUND: Radical resection is typically the standard treatment for early- and mid-stage rectal cancer as local resection may result in a high rate of recurrence and risk of distant metastasis. A growing number of studies have shown that local excision after neoadjuvant chemotherapy or chemoradiotherapy can significantly reduce recurrence rates and is a feasible strategy to preserve the rectum as an alternative to conventional radical resection. OBJECTIVE: This study aims to compare the efficacy of local resection after neoadjuvant chemotherapy or chemoradiotherapy with radical surgery for early- and mid-stage rectal cancer and to report the evidence-based clinical advantages of both techniques. METHODS: Clinical trials comparing oncologic and perioperative outcomes of local and radical resection after neoadjuvant chemotherapy or chemoradiotherapy in patients with early- to mid-stage rectal cancer were searched in PubMed, Embase, Web Of Science, and Cochrane databases, and a total of 5 randomized controlled trials and 11 cohort study trials were included. RESULTS: In terms of oncology and perioperative outcomes, there were no statistically significant differences between the radical resection group and the local resection group in terms of OS [HR = 0.99, 95%CI (0.85, 1.15), p = 0.858], DFS [HR = 1.01, 95%CI (0.64, 1.58), p = 0.967], distant metastasis rate [RR = 0.76, 95%CI (0.36,1.59), p = 0.464], and local recurrence rate [RR = 1.30, 95%CI (0.69, 2.47), p = 0.420]. However, there were significant differences in the outcomes of complications [RR = 0.49, 95% CI (0.33, 0.72), p < 0.001], length of hospital stays [WMD = - 5.13, 95%CI (- 6.22, - 4.05), p < 0.001], enterostomy [RR = 0.13, 95%CI (0.05, 0.37), p < 0.001], operative time [- 94.31, 95%CI (- 117.26, - 71.35), p < 0.001], and emotional functioning score [WMD = 2.34, 95% CI (0.94, 3.74), p < 0.001]. CONCLUSION: Local resection after neoadjuvant chemotherapy or chemoradiotherapy may be an effective alternative to radical surgery in patients with early and middle rectal cancer.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Resultado do Tratamento , Terapia Neoadjuvante/métodos , Estudos de Coortes , Estadiamento de Neoplasias , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Quimiorradioterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
IEEE J Biomed Health Inform ; 27(1): 7-16, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36306301

RESUMO

Endoscopy has been routinely used to diagnose stomach diseases including intestinal metaplasia (IM) and gastritis atrophy (GA). Such routine examination usually demands highly skilled radiologists to focus on a single patient with substantial time, causing the following two key challenges: 1) the dependency on the radiologist's experience leading to inconsistent diagnosis results across different radiologists; 2) limited examination efficiency due to the demanding time and energy consumption to the radiologist. This paper proposes to address these two issues in endoscopy using novel machine learning method in three-folds. Firstly, we build a novel and relatively big endoscopy dataset of 21,420 images from the widely used White Light Imaging (WLI) endoscopy and more recent Linked Color Imaging (LCI) endoscopy, which were annotated by experienced radiologists and validated with biopsy results, presenting a benchmark dataset. Secondly, we propose a novel machine learning model inspired by the human visual system, named as local attention grouping, to effectively extract key visual features, which is further improved by learning from multiple randomly selected regional images via ensemble learning. Such a method avoids the significant problem in the deep learning methods that decrease the resolution of original images to reduce the size of input samples, which would remove smaller lesions in endoscopy images. Finally, we propose a dual transfer learning strategy to train the model with co-distributed features between WLI and LCI images to further improve the performance. The experiment results, measured by accuracy, specificity, sensitivity, positive detection rate and negative detection rate, on IM are 99.18 %, 98.90 %, 99.45 %, 99.45 %, 98.91 %, respectively, and on GA are 97.12 %, 95.34 %, 98.90 %, 98.86 %, 95.50 %, respectively, achieving state of the art performance that outperforms current mainstream deep learning models.


Assuntos
Aprendizado Profundo , Gastrite , Humanos , Benchmarking , Endoscopia , Atrofia , Metaplasia
15.
Front Oncol ; 13: 1338060, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38162493

RESUMO

[This corrects the article DOI: 10.3389/fonc.2023.1197698.].

16.
Cells ; 11(22)2022 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-36428982

RESUMO

During disease progression and bone metastasis, breast tumor cells interact with various types of bystander cells residing in the tumor microenvironment. Such interactions prompt tumor cell heterogeneity. We used successive co-culture as an experimental model to examine cancer-bystander cell interaction. RMCF7-2, a clone of the human breast cancer MCF-7 cells tagged with a red fluorescent protein, was tracked for morphologic, behavioral, and gene expression changes. Co-cultured with various types of hematopoietic cells, RMCF7-2 adopted stable changes to a rounded shape in suspension growth of red fluorescent cells, from which derivative clones displayed marked expressional changes of marker proteins, including reduced E-cadherin and estrogen receptor α, and loss of progesterone receptor. In a successive co-culture with bone marrow-derived mesenchymal stem/stromal cells, the red fluorescent clones in suspension growth changed once more, adopting an attachment growth, but in diversified shapes. Red fluorescent clones recovered from the second-round co-culture were heterogeneous in morphology, but retained the altered marker protein expression while displaying increased proliferation, migration, and xenograft tumor formation. Interaction with bystander cells caused permanent morphologic, growth behavioral, and gene expressional changes under successive co-culture, which is a powerful model for studying cancer cell heterogeneity during breast cancer progression and metastasis.


Assuntos
Neoplasias da Mama , Células-Tronco Mesenquimais , Humanos , Feminino , Células MCF-7 , Técnicas de Cocultura , Neoplasias da Mama/patologia , Medula Óssea/patologia , Células-Tronco Mesenquimais/metabolismo , Microambiente Tumoral
17.
J Cardiothorac Surg ; 17(1): 266, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36221151

RESUMO

INTRODUCTION: The efficacy of azithromycin to prevent exacerbation for non-cystic fibrosis bronchiectasis remains controversial. We conduct this meta-analysis to explore the influence of azithromycin versus placebo for the treatment of non-cystic fibrosis bronchiectasis. METHODS: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through July 2019 for randomized controlled trials (RCTs) assessing the efficacy of azithromycin versus placebo for non-cystic fibrosis bronchiectasis. This meta-analysis was performed using the random-effect model. RESULTS: Four RCTs were included in the meta-analysis. Overall, compared with control group for non-cystic-fibrosis bronchiectasis, azithromycin treatment was associated with improved free of exacerbation (odd ratios [OR] = 3.66; 95% confidence interval [CI] = 1.69-7.93; P = 0.001), reduced pulmonary exacerbations (OR = 0.27; 95% CI 0.13-0.59; P = 0.001) and number of pulmonary exacerbations (standard mean difference [SMD] = - 0.87; 95% CI - 1.21 to - 0.54; P < 0.00001), but demonstrate no obvious impact on forced expiratory volume in 1 s (FEV1), score on St George's respiratory questionnaire, nausea or vomiting, adverse events. CONCLUSIONS: Azithromycin is effective to prevent exacerbation of non-cystic fibrosis bronchiectasis.


Assuntos
Azitromicina , Bronquiectasia , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Bronquiectasia/tratamento farmacológico , Fibrose , Volume Expiratório Forçado , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Medicine (Baltimore) ; 101(31): e27401, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35945737

RESUMO

BACKGROUND: The efficacy of alfentanil supplementation for the sedation of bronchoscopy remains controversial. We conduct a systematic review and meta-analysis to explore the influence of alfentanil supplementation on the sedation during bronchoscopy. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through December 2019 for randomized controlled trials (RCTs) assessing the effect of alfentanil supplementation versus placebo for the sedation during bronchoscopy. This meta-analysis is performed using the random-effect model. RESULTS: Five RCTs are included in the meta-analysis. Overall, compared with control group for bronchoscopy, alfentanyl supplementation is associated with significantly reduced coughing scores (Std. MD = -0.55; 95% CI = -0.96 to -0.14; P = 0.009) and dose of propofol (Std. MD = -0.34; 95% CI = -0.64 to -0.04; P = 0.03), but reveals the increase in hypoxemia (RR = 1.56; 95% CI = 1.17 to 2.08; P = 0.002). CONCLUSIONS: Alfentanyl supplementation benefits to reduce coughing scores and dose of propofol for bronchoscopy, but increases the incidence of hypoxemia. The use of alfentanyl supplementation for bronchoscopy should be with caution.


Assuntos
Propofol , Infecções Sexualmente Transmissíveis , Alfentanil , Broncoscopia , Tosse/prevenção & controle , Suplementos Nutricionais , Humanos , Hipóxia , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Eur Radiol ; 32(9): 5986-5996, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35364714

RESUMO

OBJECTIVE: To determine the ability of conventional ultrasound (US) combined with shear wave elastography (SWE) to reveal axillary status after neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: From September 2016 to December 2021, 201 patients with node-positive breast cancer who underwent NAC were enrolled in this prospective study. Conventional US features of axillary lymph nodes and SWE characteristics of breast lesions after NAC were analyzed. The diagnostic performances of US, SWE, and their combination were assessed using multivariate logistic regression and receiver operator characteristic curve (ROC) analyses. RESULTS: The area under the ROC curve (AUC) for the ability of conventional US features to determine axillary status after NAC was 0.82, with a sensitivity of 85.23%, a specificity of 67.39%, and an accuracy of 76.11%. Shear wave velocity (SWV) displayed moderate performance for predicting axilla status after NAC with SWVmean demonstrating an AUC of 0.85. Cortical thickness and shape of axillary nodes and SWVmean of breast tumors were independently associated with axillary nodal metastasis after NAC. Compared to conventional US, the combination of conventional US of axillary lymph nodes with SWE of breast lesions achieved a significantly higher AUC (0.90 vs 0.82, p < 0.01, Delong's test) with a sensitivity of 87.50%, improved specificity of 82.61% and accuracy of 85.00%. CONCLUSIONS: Breast SWE was independently associated with residual metastasis of axillary node after NAC in patients with initially diagnosed positive axilla. Combining SWE with conventional US showed good diagnostic performance for axillary node disease after NAC. KEY POINTS: • Breast SWE can serve as a supplement to axilla US for the evaluation of the axilla after NAC. • The combination of axilla US with breast SWE may be a promising method to facilitate less-invasive treatment in patients receiving NAC.


Assuntos
Neoplasias da Mama , Técnicas de Imagem por Elasticidade , Axila/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Técnicas de Imagem por Elasticidade/métodos , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/patologia , Terapia Neoadjuvante/métodos , Estudos Prospectivos
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