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1.
Dentomaxillofac Radiol ; 53(4): 222-232, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38426379

RESUMO

OBJECTIVES: Preoperative identification of different stromal subtypes of pleomorphic adenoma (PA) of the salivary gland is crucial for making treatment decisions. We aimed to develop and validate a model based on histogram analysis (HA) of ultrasound (US) images for predicting tumour stroma ratio (TSR) in salivary gland PA. METHODS: A total of 219 PA patients were divided into low-TSR (stroma-low) and high-TSR (stroma-high) groups and enrolled in a training cohort (n = 151) and a validation cohort (n = 68). The least absolute shrinkage and selection operator regression algorithm was used to screen the most optimal clinical, US, and HA features. The selected features were entered into multivariable logistic regression analyses for further selection of independent predictors. Different models, including the nomogram model, the clinic-US (Clin + US) model, and the HA model, were built based on independent predictors using logistic regression. The performance levels of the models were evaluated and validated on the training and validation cohorts. RESULTS: Lesion size, shape, cystic areas, vascularity, HA_mean, and HA_skewness were identified as independent predictors for constructing the nomogram model. The nomogram model incorporating the clinical, US, and HA features achieved areas under the curve of 0.839 and 0.852 in the training and validation cohorts, respectively, demonstrating good predictive performance and calibration. Decision curve analysis and clinical impact curves further confirmed its clinical usefulness. CONCLUSIONS: The nomogram model we developed offers a practical tool for preoperative TSR prediction in PA, potentially enhancing clinical decision-making.


Assuntos
Adenoma Pleomorfo , Nomogramas , Neoplasias das Glândulas Salivares , Ultrassonografia , Humanos , Adenoma Pleomorfo/diagnóstico por imagem , Adenoma Pleomorfo/patologia , Feminino , Neoplasias das Glândulas Salivares/diagnóstico por imagem , Neoplasias das Glândulas Salivares/patologia , Masculino , Pessoa de Meia-Idade , Ultrassonografia/métodos , Adulto , Idoso , Estudos Retrospectivos , Adolescente , Valor Preditivo dos Testes
2.
Curr Med Imaging ; 20: e15734056258908, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38087432

RESUMO

Objective: This study sought to analyze the 18F-FDG PET/CT and contrast-enhanced computed tomography (CT) images of synchronous colorectal cancer (CRC) and renal clear cell carcinoma (ccRCC) and identify the shared genes between these two types of cancer through bioinformatic analysis. Methods: A retrospective analysis was conducted on a patient with synchronous CRC and ccRCC who underwent 18F-FDG PET/CT and contrast-enhanced CT before treatment. Databases were analyzed to identify differentially expressed genes between CRC and ccRCC, and co-expression genes were extracted for RCC and CRC. Results: 18F-FDG PET/CT revealed intense metabolic activity in the primary colorectal lesion (SUVmax 13.2), while a left renal mass (diameter = 35 mm) was observed with no significant uptake. Contrast-enhanced CT during the arterial phase showed heterogeneous intense enhancement of the renal lesion, and the lesion washed out earlier than in the renal cortex in the nephrographic and excretory phases, indicating ccRCC. The histopathological results confirmed synchronous double primary malignant tumors. Our bioinformatic analysis results showed that synchronous occurrence of CRC and ccRCC may correlate with simultaneous expression of Carbonic Anhydrase 9 (CA9), integrin-binding sialoprotein (IBSP), and Fibrinogen γ chain (FGG). Conclusion: 18F-FDG PET/CT combined with contrast-enhanced CT is an effective diagnostic tool in evaluating synchronous CRC and RCC. By analyzing this clinical case and conducting bioinformatic analysis, we improved our current understanding of the mechanisms underlying synchronous tumors.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/genética , Neoplasias Renais/patologia
4.
Eur Radiol Exp ; 7(1): 72, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37985560

RESUMO

Metabolic dysfunction-associated fatty liver disease (MAFLD), previously called metabolic nonalcoholic fatty liver disease, is the most prevalent chronic liver disease worldwide. The multi-factorial nature of MAFLD severity is delineated through an intricate composite analysis of the grade of activity in concert with the stage of fibrosis. Despite the preeminence of liver biopsy as the diagnostic and staging reference standard, its invasive nature, pronounced interobserver variability, and potential for deleterious effects (encompassing pain, infection, and even fatality) underscore the need for viable alternatives. We reviewed computed tomography (CT)-based methods for hepatic steatosis quantification (liver-to-spleen ratio; single-energy "quantitative" CT; dual-energy CT; deep learning-based methods; photon-counting CT) and hepatic fibrosis staging (morphology-based CT methods; contrast-enhanced CT biomarkers; dedicated postprocessing methods including liver surface nodularity, liver segmental volume ratio, texture analysis, deep learning methods, and radiomics). For dual-energy and photon-counting CT, the role of virtual non-contrast images and material decomposition is illustrated. For contrast-enhanced CT, normalized iodine concentration and extracellular volume fraction are explained. The applicability and salience of these approaches for clinical diagnosis and quantification of MAFLD are discussed.Relevance statementCT offers a variety of methods for the assessment of metabolic dysfunction-associated fatty liver disease by quantifying steatosis and staging fibrosis.Key points• MAFLD is the most prevalent chronic liver disease worldwide and is rapidly increasing.• Both hardware and software CT advances with high potential for MAFLD assessment have been observed in the last two decades.• Effective estimate of liver steatosis and staging of liver fibrosis can be possible through CT.


Assuntos
Iodo , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Cirrose Hepática , Tomografia Computadorizada por Raios X
5.
Front Med (Lausanne) ; 9: 1005680, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457572

RESUMO

Hepatic tuberculosis (TB), which is secondary to post-hepatitis B cirrhosis, is extremely rare. We report the case of a 69-year-old man with post-hepatitis B cirrhosis complicated by primary isolated hepatic TB who was initially misdiagnosed as having hepatocellular carcinoma (HCC). The patient was hospitalized with complaints of 2 weeks of fever. He had a 20-year history of post-hepatitis B cirrhosis. The laboratory tests suggested that his serum alpha-fetoprotein (AFP) level was markedly elevated to 1210 ng/ml. From the abdominal ultrasound (US) and magnetic resonance imaging (MRI) images, we confirmed the presence of cirrhosis and discovered a space-occupying lesion of the hepatic left lobe as well as portal vein-filling defects. These results led us to consider primary liver cancer and portal vein tumor thrombus combined with decompensated cirrhosis. Biopsy and histology may be considered the ultimate diagnostic tests, but we excluded needle biopsy because of his high risk of bleeding, in addition, the patient declined the procedure. To cope with his fever, the patient was given broad-spectrum antibiotic treatment initially, followed by intravenous vancomycin. After antibiotic treatment had failed, the patient was treated with anti-TB for 10 days; after that, the patient maintained a normal temperature. The patient continued to receive tuberculostatic therapy for 6 months following his discharge. AFP completely returned to the normal level, and the aforementioned mass disappeared. Finally, hepatic TB secondary to post-hepatitis B cirrhosis with portal vein thrombosis (PVT) was considered to be the final diagnosis. More than two imaging techniques discover a space-occupying liver lesion and that the serum alpha-fetoprotein (AFP) level is extremely elevated, which means that hepatocellular carcinoma (HCC) could be diagnosed. However, some exceedingly rare diseases should not be excluded. This case illustrated that the non-invasive diagnostic criteria for liver cancer should be considered carefully when discovering a space-occupying liver lesion in a patient with cirrhosis and an elevated AFP level. In addition, primary hepatic TB should be considered and included in the differential diagnosis, and a biopsy should be performed promptly.

7.
Front Oncol ; 12: 879341, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36276079

RESUMO

Tyrosine kinase inhibitors (TKIs) are a significant treatment strategy for the management of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation status. Currently, EGFR mutation status is established based on tumor tissue acquired by biopsy or resection, so there is a compelling need to develop non-invasive, rapid, and accurate gene mutation detection methods. Non-invasive molecular imaging, such as positron emission tomography/computed tomography (PET/CT), has been widely applied to obtain the tumor molecular and genomic features for NSCLC treatment. Recent studies have shown that PET/CT can precisely quantify EGFR mutation status in NSCLC patients for precision therapy. This review article discusses PET/CT advances in predicting EGFR mutation status in NSCLC and their clinical usefulness.

8.
Nanoscale Adv ; 4(3): 952-966, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36131817

RESUMO

Liposomal nanomedicine represents a common and versatile carrier for the delivery of both lipophilic and hydrophilic drugs. However, the direct formulation of many chemotherapeutics into a liposomal system remains an enormous challenge. Using the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN38) as a model drug, we combined lipophilic prodrug construction with subsequent integration into an exogenous liposomal scaffold to assemble a prodrug-formulated liposome for systemic administration. Reconstructing SN38 with lipid cholesterol via the esterase-activatable bond endows the resulting prodrug with elevated miscibility with liposomal compositions and esterase-responsive drug release in cancerous cells. The systemic administration of the prodrug-based nanoassemblies (Chol-SN38@LP) exhibited preferential accumulation of therapeutic payloads in tumor lesions. Compared to the SN38 clinical counterpart irinotecan, our prodrug-based nanoassemblies with adaptive features showed elevated therapeutic efficacy (∼1.5 times increase of tumor inhibition) in a preclinical A549 lung carcinoma cell-derived mouse model and improved drug tolerability (i.e., alleviated bloody diarrhea and liver damage) in multiple mice models. These results may be ascribed to extended systemic circulation and preferential tumor accumulation of our nanodrugs. Hence, our findings demonstrate that rational engineering of therapeutic nanomedicine is a promising approach for effective and safe delivery of antitumor chemotherapeutics, especially to rescue drug candidates that have failed in clinical trials owing to poor PK properties or severe toxicity in patients.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(3): 695-703, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35680792

RESUMO

AbstractObjective: To explore the effect and mechanism of curcumin on human T-cell acute lymphoblastic leukemia (T-ALL) cell apoptosis induced by Mcl-1 small molecule inhibitors UMI-77. METHODS: T-ALL cell line Molt-4 was cultured, and the cells were treated with different concentrations of curcumin and Mcl-1 small molecule inhibitor UMI-77 for 24 h. The MTT method was used to detect the cell survival rate after different treatment; According to the results of curcumin and UMI-77, the experimental settings were divided into control group, curcumin group (20 µmol/L curcumin treated cells), UMI-77 group (15 µmol/L Mcl-1 small molecule inhibitor UMI-77 treated cells) and curcumin+ UMI-77 group (20 µmol/L curcumin and 15 µmol/L Mcl-1 small molecule inhibitor UMI-77 treated cells), MTT method was used to detect cell proliferation inhibition rate, Annexin V-FITC/PI double staining method and TUNEL staining were used to detect cell apoptosis, DCFH-DA probe was used to detect cell reactive oxygen species, JC-1 fluorescent probe was used to detect mitochondrial membrane potential, Western blot was used to detect the expression levels of apoptosis-related proteins and Notch1 signaling pathway-related proteins. RESULTS: After the treatment of Molt-4 cells with different concentrations of curcumin and Mcl-1 small molecule inhibitor UMI-77, the cell survival rate was decreased (P<0.05); Compared with the control group, the cell proliferation inhibition rate of the curcumin group and the UMI-77 group were increased, the apoptosis rate of cell was increased, the level of ROS was increased, the protein expression of Bax, Caspase-3 and Caspase-9 in the cells were all increased, and the protein expression of Bcl-2 was reduced (P<0.05); Compared with the curcumin group or UMI-77 group, the cell proliferation inhibition rate and apoptosis rate of the curcumin+UMI-77 group were further increased, and the level of ROS was increased. At the same time, the protein expression of Bax, Caspase-3 and Caspase-9 in the cells were all increased, the protein expression of Bcl-2 was reduced (P<0.05); In addition, the mitochondrial membrane potential of the cells after curcumin treatment was decreased, and the proteins expression of Notch1 and HES1 were reduced (P<0.05). CONCLUSION: Curcumin can enhance the apoptosis of T-ALL cells induced by Mcl-1 small molecule inhibitor UMI-77 by reducing the mitochondrial membrane potential, the mechanism may be related to the inhibition of Notch1 signaling pathway.


Assuntos
Curcumina , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Apoptose , Proteínas Reguladoras de Apoptose , Caspase 3/metabolismo , Caspase 9/metabolismo , Caspase 9/farmacologia , Linhagem Celular Tumoral , Curcumina/farmacologia , Humanos , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Sulfonamidas , Tioglicolatos , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia
10.
J Appl Microbiol ; 133(2): 1014-1026, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35543360

RESUMO

AIMS: The altered faecal metabolites and microbiota might be involved in the development of breast cancer. We aimed to investigate the effect of differential metabolites on the proliferative activity of breast cancer cells. METHODS AND RESULTS: We collected faecal samples from 14 breast cancer patients and 14 healthy subjects. Untargeted metabolomics analysis, short-chain fatty acid (SCFA) targeted analysis, and 16S rDNA sequencing was performed. The gut metabolite composition of patients changed significantly. Levels of norvaline, glucuronate and galacturonate were lower in the cancer group than in the Control (p < 0.05). 4-Methylcatechol and guaiacol increased (p < 0.05). Acetic acid and butyric acid were lower in the cancer group than in the control group (p < 0.05). Isobutyric acid and pentanoic acid were higher in the cancer group than in the control (p < 0.05). In the genus, the abundance of Rothia and Actinomyces increased in the cancer group, compared with the control group (p < 0.05). The differential microbiotas were clearly associated with differential metabolites but weakly with SCFAs. The abundance of Rothia and Actinomyces was markedly positively correlated with 4-methylcatechol and guaiacol (p < 0.05) and negatively correlated with norvaline (p < 0.05). L-norvaline inhibited the content of Arg-1 in a concentration-dependent manner. Compared with the L-norvaline or doxorubicin hydrochloride (DOX) group, the proliferation abilities of 4 T1 cells were the lowest in the L-norvaline combined with DOX (p < 0.05). The apoptosis rate increased (p < 0.05). CONCLUSIONS: Faecal metabolites and microbiota were significantly altered in breast cancer. Levels of differential metabolites (i.e. Norvaline) were significantly correlated with the abundance of differential microbiota. L-norvaline combined with DOX could clearly inhibit the proliferation activity of breast cancer cells. SIGNIFICANCE AND IMPACT OF STUDY: This might provide clues to uncover potential biomarkers for breast cancer diagnosis and treatment.


Assuntos
Neoplasias da Mama , Microbioma Gastrointestinal , Microbiota , Ácido Butírico/farmacologia , Proliferação de Células , Fezes , Feminino , Guaiacol/farmacologia , Humanos , Metaboloma , Valina/análogos & derivados
11.
Front Med (Lausanne) ; 9: 839954, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386919

RESUMO

Several cases of pigmented mammary Paget's disease (PMPD) mimicking cutaneous malignant melanoma have been reported. In these cases, the tumor cells are colonized by melanocytes, particularly with the presence of a population of melanocytes staining for HMB-45 and S100. Here, we report a case of mammary Paget disease (MPD) which was misdiagnosed as melanoma in situ due to the interpretation of the staining of melanocytic markers S-100, Melan-A, and HMB-45. The tumor cells strongly expressed CK7 and GATA3, and a dual-labeling showed negative PHH3 labeling for the melanocytes. Pathologists need to be aware of the caveat of colonization of melanocytes in Paget disease.

12.
Eur J Cancer ; 161: 10-22, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896904

RESUMO

BACKGROUND: Chemotherapy-related cognitive impairment (CRCI) is highly prevalent in patients with cancer and is associated with poor outcomes and quality of life. To date, the management of CRCI remains a clinical challenge. Herein, we aim to determine the preventive effects of probiotics on CRCI development and underlying mechanisms. METHODS: We conducted a randomised, double-blind and placebo-controlled trial (ChiCTR-INQ-17014181) of 159 patients with breast cancer and further investigated the underlying mechanism in a pre-clinical setting. From 2018 to 2019, patients with breast cancer (Stage I-III) who needed adjuvant chemotherapy were screened, enrolled and randomly assigned to receive either probiotics or placebo (three capsules, twice/day) during chemotherapy. Their cognition, anxiety and depression were assessed with well-established assays; their plasma biomarkers, metabolites and faecal microbiota compositions were measured. In addition, the systemic effects of the metabolites found in the clinical trial on long-term potentiation, synapse injury, oxidative stress and glial activation were assessed in rats. RESULTS: Probiotics supplement significantly decreased the incidence of CRCI, improved the allover cognitive functions, changed the gut microbial composition and modulated nine plasma metabolite changes. Among these metabolites, p-Mentha-1,8-dien-7-ol, Linoelaidyl carnitine and 1-aminocyclopropane-1-carboxylic acid were negatively correlated with the occurrence of CRCI. Furthermore, probiotics supplement increased plasma p-Mentha-1,8-dien-7-ol in rats. Administration of exogenous p-Mentha-1,8-dien-7-ol significantly alleviated chemotherapy-induced long-term potentiation impairment, synapse injury, oxidative stress and glial activation in the hippocampus of rats. CONCLUSION: Our data indicated that probiotics supplement prevents the occurrence of CRCI in patients with breast cancer via modulating plasma metabolites, including p-Mentha-1,8-dien-7-ol. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-INQ-17014181) [http://www.chictr.org.cn/showproj.aspx?proj=24294].


Assuntos
Neoplasias da Mama/complicações , Comprometimento Cognitivo Relacionado à Quimioterapia/tratamento farmacológico , Probióticos/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Probióticos/farmacologia , Estudos Prospectivos , Adulto Jovem
13.
Biosci Rep ; 42(1)2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-34935899

RESUMO

Due to the lack of known therapeutic targets for triple-negative breast cancer (TNBC), chemotherapy is the only available pharmacological treatment. Pirarubicin (tetrahydropyranyl Adriamycin, THP) is the most commonly used anthracycline chemotherapy agent. However, TNBC has a high recurrence rate after chemotherapy, and the mechanisms of chemoresistance and recurrence are not entirely understood. To study the chemoresistance mechanisms, we first screened compounds on a pirarubicin-resistant cell line (MDA-MB-231R) derived from MDA-MB-231. The drug resistance index of MDA-MB-231R cells was approximately five times higher than that of MDA-MB-231 cells. MDA-MB-231R cells have higher GRP78 and lower miR-495-3p expression levels than MDA-MB-231 cells. Transfecting MDA-MB-231R cells with a siGRP78 plasmid reduced GRP78 expression, which restored pirarubicin sensitivity. Besides, transfecting MDA-MB-231R cells with miR-495-3p mimics increased miR-495-3p expression, which also reversed pirarubicin chemoresistance. Cell counting kit-8 (CCK-8), EdU, wound healing, and Transwell assays showed that the miR-495-3p mimics also inhibited cell proliferation and migration. Based on our results, miR-495-3p mimics could down-regulate GRP78 expression via the p-AKT/mTOR signaling pathway in TNBC cells. Remarkably, chemo-resistant and chemo-sensitive TNBC tissues had opposite trends in GRP78 and miR-495-3p expressions. The lower the GRP78 and the higher the miR-495-3p expression, the better prognosis in TNBC patients. Therefore, the mechanism of pirarubicin resistance might involve the miR-495-3p/GRP78/Akt axis, which would provide a possible strategy for treating TNBC.


Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Chaperona BiP do Retículo Endoplasmático/metabolismo , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Chaperona BiP do Retículo Endoplasmático/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Fosforilação , Transdução de Sinais , Neoplasias de Mama Triplo Negativas/enzimologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
14.
Mol Ther Oncolytics ; 23: 515-530, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34901393

RESUMO

Metastasis is considered the leading cause of cancer death due to the limited possibilities to therapeutically target this process. How the ubiquitination machinery contributes to metastasis remains underexplored. Angio-associated migratory cell protein (AAMP), a ubiquitously expressed protein involved in cell migration, has been reported to play oncogenic roles in breast and non-small cell lung cancer (NSCLC). However, the role of AAMP in colorectal cancer (CRC) has not been demonstrated. Here, we report that AAMP is aberrantly upregulated in metastatic CRC and that AAMP upregulation is correlated with the poor survival of CRC patients. AAMP knockdown significantly attenuated the migration and invasion of CRC cells, while AAMP overexpression led to the opposite effects. Mechanistically, we identified Ras homolog family member A (RhoA) as a target of AAMP. Smad ubiquitin regulatory factor (SMURF) 2 was previously found to be a CRC suppressor. Notably, we discovered here that SMURF2 acted as an E3 ubiquitin ligase to mediate the ubiquitination and degradation of RhoA. AAMP stabilized RhoA by binding to it and suppressing its SMURF2-mediated ubiquitination and degradation. Subsequently, the level of active RhoA was increased, thereby accelerating CRC cell migration and invasion. These findings indicate a new potential antitumor target for CRC.

15.
Breast Care (Basel) ; 16(4): 328-334, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34602938

RESUMO

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) and stromal tumor-infiltrating lymphocytes (sTILs) are associated with immunogenicity and prognosis of patients with triple-negative breast cancer (TNBC). OBJECTIVE: To investigated the prognostic roles of NLR and sTILs and their rela-tionship of TNBC patients treated with neoadjuvant chemotherapy (NAC). METHODS: The clinical data of 170 patients with locally advanced TNBC who received NAC from January 2010 to December 2014 were collected. The difference among variables was calculated by χ2 test. The association between essential clinicopathological characteristics, pathological complete response (pCR), NLR, and sTILs with disease-free survival (DFS) was analyzed. Kaplan-Meier and Cox analysis were performed to address the effects of clinical parameters on prognosis. RESULTS: There was a trend that TNBC patients with lower baseline NLR (NLR1) or higher sTILs scoring would obtain a better pCR rate. NLR1 and sTILs were not associated (p > 0.05). Patients with low NLR1 or high sTILs scoring had a significantly improved DFS compared to those with high NLR1 or low sTILs scoring (p = 0.002 and p = 0.001, respectively). The increased lymphocyte count in peripheral blood after NAC was associated with the improved DFS outcome in both high and low NLR1 groups. Cox analysis revealed that NLR1 and sTILs were independent prognostic predictors of DFS outcome (p < 0.001). CONCLUSION: Low NLR1 and high sTILs were associated with better DFS outcome in locally advanced TNBC patients treated with NAC. Further studies are needed to explore the connection between systemic and local inflammatory/immune markers.

16.
Front Cell Dev Biol ; 9: 681240, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34350177

RESUMO

Background: An increasing number of studies have shown that Isthmin 1 (ISM1), a secreted protein, is important in tumorigenesis and invasion, including in colorectal cancer (CRC). However, the mechanisms are still unclear. This study aims to explore the function and prognosis capacity of ISM1 in CRC. Methods: We investigated the expression of ISM1 in 18 CRC tissues vs. adjacent normal tissues from GSE50760, 473 CRC tissues vs. 41 normal tissues from The Cancer Genome Atlas (TCGA), and across gastrointestinal cancer types. Differences were further confirmed in CRC tissues via quantitative real-time polymerase chain reaction (qRT-PCR). Then, we analyzed correlations between clinicopathologic features and ISM1 expression, including prognostic prediction value, using the Kaplan-Meier method and multivariate Cox regression. Gene set enrichment analysis (GSEA) was performed to identify ISM1-related pathways. In vitro experiments were performed to verify the role of ISM1 in epithelial-mesenchymal transition (EMT) and CRC progression. Results: Multiple datasets showed that ISM1 is upregulated in CRC tissues, which was validated. Patients with higher ISM1 expression had shorter overall survival (OS), and ISM1 expression served as an independent prognostic factor. Enrichment analysis showed that ISM1 upregulation was positively correlated with cancer-related pathways, such as EMT, hypoxia, and the Notch and KRAS signaling pathways. We were exclusively interested in the connection between ISM1 and EMT because 71% of genes in this pathway were significantly positively co-expressed with ISM1, which may account for why patients with higher ISM1 expression are prone to regional lymph node involvement and progression to advanced stages. In addition, we found that ISM1 was positively correlated with multiple immunosuppressive pathways such as IL2/STAT5, TNF-α/NF-κB, and TGF-ß, and immune checkpoints, including PD-L1, PD-1, CTLA-4, and LAG3, which may account for upregulation of ISM1 in immunotherapy-resistant patients. Notably, through in vitro experiments, we found that ISM1 promoted EMT and colon cancer cell migration and proliferation. Conclusion: ISM1 is critical for CRC development and progression, which enhances our understanding of the low response rate of CRC to immunotherapy via immunosuppressive signaling pathways.

17.
World J Surg Oncol ; 19(1): 148, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980267

RESUMO

BACKGROUND: The aim of this study was to compare conventional suture with prolonged timing of drainage with quilting suture on the formation of seroma at pectoral area after mastectomy (ME) with sentinel lymph node biopsy (SLN) or axillary lymph node dissection (ALND) for breast cancer. METHODS: Three hundred and eighty-eight consecutive breast cancer patients were retrospectively analyzed and categorized into three groups. Patients in group 1 were with quilting suture, group 2 with conventional suture and 13-15 days drainage in situ, and group 3 with conventional suture and 20-22 days drainage. The primary outcome was the incidence of grades 2 and 3 seroma at anterior pectoral area within 1 month postoperatively. Cox regression was used for analysis. RESULTS: The incidence of grades 2 and 3 seroma was comparable among groups (9.5% vs. 7.9% vs. 5.3%, p = 0.437), as well as late grades 2 and 3 seroma among groups (4.3% vs. 2.9% vs. 1.5%, p = 0.412). Old age, high body mass index, and hypertension were independent risk factors for grades 2 and 3 seroma. CONCLUSIONS: Prolonged timing of drainage to 13-15 days in conventional suture was long enough to decrease the incidence of grades 2 and 3 seroma as lower as that in quilting suture group at pectoral area within 1 month after mastectomy.


Assuntos
Neoplasias da Mama , Seroma , Neoplasias da Mama/cirurgia , Drenagem , Humanos , Excisão de Linfonodo/efeitos adversos , Mastectomia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Prognóstico , Estudos Retrospectivos , Seroma/etiologia , Seroma/prevenção & controle , Retalhos Cirúrgicos , Técnicas de Sutura , Suturas
18.
BMC Cardiovasc Disord ; 21(1): 204, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888070

RESUMO

BACKGROUND: The purpose of the study is to identify off-pump patients who are at higher risk of mortality after re-exploration for bleeding or tamponade. METHODS: We analyzed the data of 3256 consecutive patients undergoing isolated off-pump coronary artery bypass grafting (OPCABG) in our heart center from 2013 through 2020. Fifty-eight patients underwent re-exploration after OPCABG. The 58 patients were divided into death group and survival group according to their discharge status. Propensity score matching (PSM) was performed to analysis the risk factors of death. 15 pairs of cases of two groups were matched well. RESULTS: The mortality rate of patients underwent re-exploration after OPCABG for bleeding or tamponade was 27.59% (16/58). In the raw data, we found the patients in death group had higher body mass index (BMI) (P = 0.030), higher cardiac troponin T (cTnT) (P = 0.028) and higher incidence of heart failure before OPCABG (P = 0.003). After PSM, the levels of lactic acid before and after re-exploration (P = 0.028 and P < 0.001) were higher in death group. And the levels of creatinine (P = 0.002) and cTnT (P = 0.017) were higher in the death group after re-exploration. The death group had longer reoperation time (P = 0.010). In addition, the perioperative utilization rate of intra-aortic ballon pump (IABP) (P = 0.027), continuous renal replacement therapy (CRRT) (P < 0.001) and platelet transfusion (P = 0.017) were higher than survival group. CONCLUSIONS: The mortality rate of patients undergoing re-exploration for bleeding or tamponade after isolated OPCABG is high. More attention should be paid to patients with above risk factors and appropriate measures should be taken in time.


Assuntos
Tamponamento Cardíaco/cirurgia , Ponte de Artéria Coronária sem Circulação Extracorpórea/mortalidade , Doença da Artéria Coronariana/cirurgia , Hemorragia Pós-Operatória/cirurgia , Reoperação/mortalidade , Idoso , Tamponamento Cardíaco/diagnóstico por imagem , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/mortalidade , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/diagnóstico por imagem , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/mortalidade , Reoperação/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
19.
Klin Padiatr ; 233(2): 63-68, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33684950

RESUMO

OBJECTIVE: To summarize the clinical features of primary nephrotic syndrome (PNS) complicated by plastic bronchitis (PB) in children to provide guidance for treatment. METHODS: We conducted a retrospective review of the clinical data of 25 children hospitalized with NS complicated by PB in our Hospital between 10/2016 and 03/2019, and summarized the clinical manifestations, imaging and fiberoptic bronchoscopy (FOB) examinations, treatment course and outcome of them. RESULTS: 1). The 25 children, with a nephrotic syndrome (NS) course of one to 36 months, were all diagnosed with PB after FOB, among which 8 cases (32%) had respiratory failure and required ventilatory support. All of them started with respiratory symptoms such as fever and cough, and then suffered from dyspnea and progressive aggravation after 1-3 day(s) of onset, with rapid occurrence of bidirectional dyspnea and even respiratory failure in severe cases. 2). Laboratory test for pathogens: influenza A virus H1N1 (11 cases), influenza B virus (9 cases), adenovirus (3 cases) and mycoplasma pneumoniae (2 cases). There was no statistically significant difference (P>0.05) between children with common NS complicated by influenza virus (IV) infection (not accompanied by dyspnea) and those with kidney disease who developed PB in the white blood cell count, lymphocyte count, the inflammatory biomarkers C-reactive protein (CRP), procalcitonin (PCT) and humoral immunity (IgG level), yet the total IgG level was found significantly higher and the blood albumin level lower in the latter (P<0.05). 3). The 25 children were all examined with the FOB and treated with lavage, 15 of which had typical bronchial tree-like casts and 10 broken and stringy casts. Based on histopathological classification, all children were of Type I. 4). Twenty children (80%) with influenza were administered the antiviral drug Oseltamivir, 20 (80%) were treated with antibiotics, oral hormones were replaced with the same dosage of intravenous Methylprednisolone for 5 cases (20%), and 20 (80%) were intravenously administered gamma globulins (400-500 mg/kg x 3 days). These children showed a remarkable improvement after treatment and there were no deaths. CONCLUSION: NS children are at high risk of influenza virus infection. Children with a severe case of NS are more susceptible to PB. If symptoms like shortness of breath, wheezing and progressive bidirectional dyspnea occur, FOB examination and lavage treatment should be performed as early as possible. Hyper-IgE-emia and hypoproteinemia may be the high risk factors for PNS complicated by PB in children. ZIEL: Ziel der Studie war es, durch Zusammenfassung der klinischen Merkmale des primären nephrotischen Syndroms (PNS) mit komplizierender plastischer Bronchitis (PB) im Kindesalter eine Orientierungshilfe für die Therapie der Erkrankung zu geben. METHODIK: Wir führten eine retrospektive Prüfung der klinischen Daten von 25 Kindern durch, die zwischen Oktober 2016 und März 2019 in unser Krankhaus aufgenommen wurden, und erstellten eine Zusammenfassung der klinischen Symptome, Untersuchungen mit bildgebenden Verfahren und fiberoptischer Bronchoskopie (FOB), des Therapieverlaufs und des Outcomes der Patienten. ERGEBNISSE: 1). Bei den 25 Kindern bestand ein nephrotisches Syndrom (NS) über einen Zeitraum von einem bis 36 Monaten. Bei allen Patienten wurde die Diagnose PB nach FOB gestellt, wobei in 8 Fällen (32%) eine beatmungspflichtige respiratorische Insuffizienz vorlag. Alle Patienten zeigten anfänglich Symptome einer Atemwegserkrankung wie Fieber und Husten, gefolgt von Atemnot und progredienter Verschlechterung 1 bis 3 Tage nach Erkrankungsbeginn. Dabei kam es rasch zum Auftreten bidirektionaler Atemnot, in schweren Fällen bis hin zur respiratorischen Insuffizienz. 2). Laboruntersuchung auf Erreger: Influenza-A-Virus H1N1 (11 Fälle), Influenza-B-Virus (9 Fälle), Adenovirus (3 Fälle) und Mycoplasma pneumoniae (2 Fälle). Es fand sich kein statistisch signifikanter Unterschied (P>0,05) zwischen Kindern, die ein "gewöhnliches" NS mit komplizierender Influenza-Virus (IV)-Infektion (ohne begleitende Atemnot) aufwiesen, und Kindern mit Nierenerkrankung, die eine PB entwickelten, hinsichtlich der Leukozyten- und Lymphozytenwerte sowie der Entzündungsmarker C-reaktives Protein (CRP), Procalcitonin (PCT) und humorale Immunität (IgG-Wert). Allerdings wurde bei der letzteren Patientengruppe ein signifikant höherer Gesamt-IgG-Wert und ein signifikant niedriger Albumin-Spiegel im Blut nachgewiesen (P<0.05). 3). Bei allen 25 Kindern erfolgte eine FOB und Therapie mit Lavage, bei 15 Kinder fanden sich typische verzweigte Ausgüsse der Bronchialäste und bei 10 Patienten desintegrierte und zähe Ausgüsse. Gemäß der histopathologischen Klassifikation waren alle Kinder vom Typ I. 4). Zwanzig Kinder (80%) mit Influenza erhielten das Virostatikum Oseltamivir, 20 Kinder (80%) eine Antibiotikatherapie, in 5 Fällen (20%) wurden oral gegebene Hormone durch intravenös in derselben Dosis verabreichtes Methylprednisolon ersetzt und 20 Kinder (80%) erhielten intravenös verabreichte Gammaglobuline (400-500 mg/kg Körpergewicht x 3 Tage). Diese Kinder zeigten eine bemerkenswerte Verbesserung nach der Therapie und es traten keine Todesfälle auf. SCHLUSSFOLGERUNG: Bei Kindern mit NS besteht ein hohes Risiko für eine Influenza-Virus-Infektion. Kinder mit schwerem NS sind anfälliger für PB. Bei Auftreten von Symptomen wie Atemnot, Giemen und Brummern sowie progredienter bidirektionaler Dyspnoe sollte baldmöglichst eine FOB-Untersuchung und eine therapeutische Lavage durchgeführt werden. Erhöhte IgE-Werte im Blut und Hypoproteinämie stellen möglicherweise Risikofaktoren für PNS mit komplizierender PB im Kindesalter dar.


Assuntos
Bronquite , Vírus da Influenza A Subtipo H1N1 , Síndrome Nefrótica , Bronquite/diagnóstico , Bronquite/tratamento farmacológico , Criança , Humanos , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Plásticos , Estudos Retrospectivos
20.
BMC Surg ; 20(1): 65, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252732

RESUMO

BACKGROUND: The aim of this study was to compare quilting suture with conventional suture on the formation of seroma at pectoral area after mastectomy (ME) with sentinel lymph nodes biopsy (SLN) or axillary lymph nodes dissection (ALND) for breast cancer. METHODS: Two hundred thirty-five consecutive breast cancer patients were retrospectively analyzed. The primary outcome was the incidence of Grade 2 or Grade 3 seroma at anterior pectoral area within 1 month postoperatively. We categorized seroma into early or late seroma according to the drainage removal time. Cox regression was used for analysis. RESULTS: The incidence of Grade 2 and 3 seroma was significantly higher in the conventional suture group compared with that in the quilting suture group (19.3% vs. 9.5%, p = 0.032), which was attributed to the late seroma in Grade 2 and 3. Quilting suture was associated with longer time for fixing flaps compared with that of conventional suture (504.7 s vs. 109.1 s, p < 0.001), but with less volume of drainage. Old age, high body mass index and conventional suture were independently risk factors for Grade 2 and 3 seroma. CONCLUSIONS: Quilting suture decreased the incidence of Grade 2 and 3 seroma at pectoral area within 1 month after mastectomy, especially the late seroma in Grade 2 and 3.


Assuntos
Neoplasias da Mama/cirurgia , Mastectomia/métodos , Complicações Pós-Operatórias/prevenção & controle , Seroma/etiologia , Adulto , Drenagem/efeitos adversos , Drenagem/métodos , Feminino , Humanos , Incidência , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Retalhos Cirúrgicos/efeitos adversos , Técnicas de Sutura/efeitos adversos , Suturas/efeitos adversos
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