RÉSUMÉ
Neutrophils are recognized active participants in inflammatory responses and are intricately linked to cancer progression. In response to inflammatory stimuli, neutrophils become activated, releasing neutrophils extracellular traps (NETs) for the capture and eradication of pathogens, a phenomenon termed NETosis. With a deeper understanding of NETs, there is growing evidence supporting their role in cancer progression and their involvement in conferring resistance to various cancer therapies, especially concerning tumor reactions to chemotherapy, radiation therapy (RT), and immunotherapy. This review summarizes the roles of NETs in the tumor microenvironment (TME) and their mechanisms of neutrophil involvement in the host defense. Additionally, it elucidates the mechanisms through which NETs promote tumor progression and their role in cancer treatment resistance, highlighting their potential as promising therapeutic targets in cancer treatment and their clinical applicability.
RÉSUMÉ
BACKGROUND: Malignant phyllodes tumors (MPTs) are rare breast tumors with high risks of local recurrence and distant metastasis. Surgical intervention is the primary treatment, but the effectiveness of adjuvant therapies is uncertain. This study was designed to analyze the prognostic risk factors associated with MPTs and evaluate the efficacy of postoperative adjuvant chemotherapy. PATIENTS AND METHODS: Patients who were first diagnosed with MPT without distant metastasis and received R0 resection surgery between 1999 and 2023 were included in the present study and stratified into 2 groups: chemotherapy and nonchemotherapy groups. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate local recurrence-free survival (LRFS) and overall survival (OS). Cox proportional hazards analyses (univariate and multivariate) were conducted to identify prognostic risk factors. RESULTS: We conducted a study involving 145 patients, 31 of whom underwent a total of 12 different chemotherapy regimens following initial surgical resection. Most patients received chemotherapy regimens primarily consisting of anthracyclines, including anthracycline + ifosfamide (AI) or anthracycline + cyclophosphamide/docetaxel (AC-T) regimens. After a median follow-up of 54.5 months, 37 (25.5%) patients experienced local recurrence and 24 (16.6%) experienced distant metastasis. No significant difference was detected in the rates of local recurrence or distant metastasis between the 2 groups. Axillary lymph node positivity was the only risk factor for LRFS, whereas older age, larger tumors, axillary lymph node positivity, local recurrence, and distant metastasis were significantly associated with worse OS. Chemotherapy did not emerge as a protective factor for LRFS (P=.501) or OS (P=.854). After PSM, patients in the chemotherapy group did not exhibit better 5-year LRFS (P=.934) or 5-year OS (P=.328). CONCLUSIONS: According to our retrospective evaluation, postoperative adjuvant chemotherapy was not associated with improved survival in patients with MPTs without distant metastasis.
RÉSUMÉ
Contrast-enhanced ultrasound (CEUS) plays a crucial role in cancer diagnosis. The use of ultrasound contrast agents (UCAs) is inevitable in CEUS. However, current applications of UCAs primarily focus on enhancing imaging quality of ultrasound contrast rather than serving as integrated platforms for both diagnosis and treatment in clinical settings. In this study, a novel UCA, termed NPs-DPPA(C3F8), is innovatively prepared using a combination of nanoprecipitation and ultrasound vibration methods. The DPPA lipid possesses inherent antiangiogenic and antitumor activities, and when combined with C3F8, it functions as a theranostic agent. Notably, the preparation of NPs-DPPA(C3F8) is straightforward, requiring only one hour from raw materials to the final product due to the use of a single material, DPPA. NPs-DPPA(C3F8) exhibits inherent antiangiogenic and biotherapeutic activities, effectively inhibiting triple-negative breast cancer (TNBC) angiogenesis and reducing VEGFA expression both in vitro and in vivo. Clinically, NPs-DPPA(C3F8) enables simultaneous real-time imaging, tumor assessment, and antitumor activity. Additionally, through ultrasound cavitation, NPs-DPPA(C3F8) can overcome the dense vascular walls to increase accumulation at the tumor site and facilitate internalization by tumor cells. The successful preparation of NPs-DPPA(C3F8) offers a novel approach for integrating clinical diagnosis and treatment of TNBC.
RÉSUMÉ
Long non-coding RNAs (lncRNAs) are a class of RNA transcripts more than 200 nucleotides in length that play crucial roles in cancer development and progression. With the rapid development of high-throughput sequencing technology, a considerable number of lncRNAs have been identified as novel biomarkers for predicting the prognosis of cancer patients and/or therapeutic targets for cancer therapy. In recent years, increasing evidence has shown that the biological functions and regulatory mechanisms of lncRNAs are closely associated with their subcellular localization. More importantly, based on the important roles of lncRNAs in regulating cancer progression (e.g., growth, therapeutic resistance, and metastasis) and the specific ability of nucleic acids (e.g., siRNA, mRNA, and DNA) to regulate the expression of any target genes, much effort has been exerted recently to develop nanoparticle (NP)-based nucleic acid delivery systems for in vivo regulation of lncRNA expression and cancer therapy. In this review, we introduce the subcellular localization and regulatory mechanisms of various functional lncRNAs in cancer and systemically summarize the recent development of NP-mediated nucleic acid delivery for targeted regulation of lncRNA expression and effective cancer therapy.
RÉSUMÉ
Emerging evidence shows that the biomechanical environment is required to support cancer stem cells (CSCs), which play a crucial role in drug resistance. However, how mechanotransduction signals regulate CSCs and its clinical significance has remained unclear. Using clinical-practice ultrasound elastography for patients' lesions and atomic force microscopy for surgical samples, we reveal that increased matrix stiffness is associated with poor responses to neoadjuvant chemotherapy, worse prognosis, and CSC enrichment in patients with breast cancer. Mechanically, TAZ activated by biomechanics enhances CSC properties via phase separation with NANOG. TAZ-NANOG phase separation, which is dependent on acidic residues in the N-terminal activation domain of NANOG, promotes the transcription of SOX2 and OCT4. Therapeutically, targeting NANOG or TAZ reduces CSCs and enhances the chemosensitivity in vivo. Collectively, this study demonstrated that the phase separation of a pluripotency transcription factor links mechanical cues in the niche to the fate of CSCs.
Sujet(s)
Tumeurs du sein , Mécanotransduction cellulaire , Protéine homéotique Nanog , Transcriptional coactivator with PDZ-binding motif proteins , Femelle , Humains , Tumeurs du sein/génétique , Tumeurs du sein/anatomopathologie , Lignée cellulaire tumorale , Protéine homéotique Nanog/génétique , Cellules souches tumorales/anatomopathologie , Facteurs de transcription/génétique , Transcriptional coactivator with PDZ-binding motif proteins/génétique , Niche de cellules souchesRÉSUMÉ
As a common female malignancy, triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancers (BC). This study further studied the role of long noncoding RNA (lncRNA) prostate cancer-associated transcript 6 (PCAT6) in TNBC. Functional assays, including EdU, wound healing, transwell, and immunofluorescence staining, revealed the effect of PCAT6 on cell proliferation, migration, and EMT process. The tube-formation assay disclosed the function of PCAT6 on angiogenesis. In vivo assays were also established to explore the impact of PCAT6 on tumor growth and microangiogenesis. The results revealed that PCAT6 boosted TNBC cell proliferation, migration, and angiogenesis both in vitro and in vivo. Then, this study unveiled that M2 macrophage secreted VEGF to stimulate the upregulation of PCAT6, thus promoting angiogenesis in TNBC. Next, through bioinformatics analysis and mechanism assays, we identified that PCAT6 positively regulated VEGFR2 expression via ceRNA pattern and then participated in VEGFR/AKT/mTOR signaling pathway to accelerate angiogenesis. Moreover, PCAT6 bound USP14, a deubiquitinase, to induce the deubiquitination of VEGFR2. On the whole, M2 macrophage-induced upregulation of PCAT6 facilitates TNBC tumorigenesis through modulation of VEGFR2 expression via ceRNA and deubiquitination patterns.
Sujet(s)
Macrophages/métabolisme , ARN long non codant/métabolisme , Tumeurs du sein triple-négatives/vascularisation , Récepteur-2 au facteur croissance endothéliale vasculaire/métabolisme , Animaux , Carcinogenèse , Femelle , Humains , Mâle , Souris , Souris nude , Néovascularisation pathologique/métabolisme , Néovascularisation pathologique/anatomopathologie , Transfection , Tumeurs du sein triple-négatives/génétique , Tumeurs du sein triple-négatives/métabolisme , Tumeurs du sein triple-négatives/anatomopathologieRÉSUMÉ
Though radiofrequency ablation (RFA) is considered to be an effective treatment for hepatocellular carcinoma (HCC), but more than 30% of patients may suffer insufficient RFA (IRFA), which can promote more aggressive of the residual tumor. One possible method to counter this is to accurately identify the margin of the HCC. Colony-stimulating factor 1 receptor (CSF-1R) has been found to be restrictively expressed by tumor associated macrophages (TAMs) and monocytes which more prefer to locate at the boundary of HCC. Using biotinylation method, we developed a CSF-1R-conjugated nanobubble CSF-1R (NBCSF-1R) using a thin-film hydration method for margin detection of HCC. CSF-1R expression was higher in macrophages than in HCC cell lines. Furthermore, immunofluorescence showed that CSF-1R were largely located in the margin of xenograft tumor and IFRA models. In vitro, NBCSF-1R was stable and provided a clear ultrasound image even after being stored for 6 months. In co-culture, NBCSF-1R adhered to macrophages significantly better than HCC cells (p = 0.05). In in vivo contrast-enhanced ultrasound imaging, the washout half-time of the NBCSF-1R was significantly greater than that of NBCTRL and Sonovue® (p = 0.05). The signal intensity of the tumor periphery was higher than the tumor center or non-tumor region after NBCSF-1R injection. Taken together, NBCSF-1R may potentially be used as a non-invasive diagnostic modality in the margin detection of HCC, thereby improving the efficiency of RFA. This platform may also serve as a complement method to detect residual HCC after RFA; and may also be used for targeted delivery of therapeutic drugs or genes.
RÉSUMÉ
OBJECTIVE: To evaluate the combined use of strain elastography (SE) and superb microvascular imaging (SMI) with grayscale ultrasound (US) according to the Breast Imaging Reporting and Data System (BI-RADS) classification for differentiating benign from malignant breast masses. METHODS: In total, 166 patients with 177 breast masses categorized as BI-RADS 3-5 were included in the study between April 2016 to September 2017. US, SMI and SE were performed to evaluate each mass. The following outcome measures were compared between US and the combinations of US, SMI, and SE: area under the receiver operating characteristic curve (AUC), sensitivity, specificity. RESULTS: The addition of SMI and SE to US increased the AUC from 0.816 to 0.948 (Pâ<â.001); and the specificity from 43.7% to 80.8% (Pâ<â.001), without a significant decrease in the sensitivity. Meanwhile, 66.1% (37 of 56) of the benign masses that were indicated for unnecessary biopsy were correctly changed to follow-up. CONCLUSIONS: The addition SMI and SE to US could improve the diagnostic performance in differentiating benign from malignant breast masses compared to US alone. When US was combined with SMI and SE, the specificity were increased, thus significantly reducing unnecessary biopsies.
Sujet(s)
Tumeurs du sein/imagerie diagnostique , Région mammaire/anatomopathologie , Imagerie d'élasticité tissulaire/méthodes , Échographie mammaire/méthodes , Échographie/méthodes , Adulte , Sujet âgé , Tumeurs du sein/anatomopathologie , Femelle , Humains , Adulte d'âge moyen , Études prospectivesRÉSUMÉ
Chimeric antigen receptor (CAR) T cell is a novel approach, which utilizes anti-tumor immunity for cancer treatment. As compared to the traditional cell-mediated immunity, CAR-T possesses the improved specificity of tumor antigens and independent cytotoxicity from major histocompatibility complex molecules through a monoclonal antibody in addition to the T-cell receptor. CAR-T cell has proven its effectiveness, primarily in hematological malignancies, specifically where the CD 19 CAR-T cells were used to treat B-cell acute lymphoblastic leukemia and B-cell lymphomas. Nevertheless, there is little progress in the treatment of solid tumors despite the fact that many CAR agents have been created to target tumor antigens such as CEA, EGFR/EGFRvIII, GD2, HER2, MSLN, MUC1, and other antigens. The main obstruction against the progress of research in solid tumors is the tumor microenvironment, in which several elements, such as poor locating ability, immunosuppressive cells, cytokines, chemokines, immunosuppressive checkpoints, inhibitory metabolic factors, tumor antigen loss, and antigen heterogeneity, could affect the potency of CAR-T cells. To overcome these hurdles, researchers have reconstructed the CAR-T cells in various ways. The purpose of this review is to summarize the current research in this field, analyze the mechanisms of the major barriers mentioned above, outline the main solutions, and discuss the outlook of this novel immunotherapeutic modality.
Sujet(s)
Antigènes néoplasiques/métabolisme , Tumeurs/thérapie , Récepteurs chimériques pour l'antigène/métabolisme , Lymphocytes T/immunologie , Animaux , Antigènes néoplasiques/génétique , Marqueurs biologiques tumoraux , Cytokines/métabolisme , Édition de gène , Thérapie génétique/méthodes , Humains , Immunothérapie adoptive/méthodes , Mésothéline , Tumeurs/génétique , Tumeurs/immunologie , Récepteurs chimériques pour l'antigène/génétique , Protéines de fusion recombinantes/immunologie , Microenvironnement tumoralRÉSUMÉ
BACKGROUND: RNA helicases have various essential functions in basically all aspects of RNA metabolism, not only unwinding RNA but also disturbing the interaction of RNA with proteins. Recently, RNA helicases have been considered potential targets in cancers. So far, there has been no detailed investigation of the biological functions of RNA helicase DHX37 in cancers. OBJECTIVE: We aim to identify the prognostic value of DHX37 associated with tumor microenvironments in cancers. METHODS: DHX37 expression was examined via the Oncomine database and Tumor Immune Estimation Resource (TIMER). We explored the prognostic role of DHX37 in cancers across various databases. Coexpression genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and fundamental regulators were performed via LinkedOmics. Confirming the prognostic value of DHX37 in liver hepatocellular carcinoma (LIHC) and lung adenocarcinoma (LUAD), we explored the role of DHX37 in infiltrated lymphocytes in cancers using the Gene Expression Profiling Interactive Analysis (GEPIA) and TIMER databases. RESULTS: Through GO and KEGG analyses, expression of DHX37 was also correlated with complex function-specific networks involving the ribosome and RNA metabolic signaling pathways. In LIHC and LUAD, DHX37 expression showed significant positive correlations with markers of Tregs, myeloid-derived suppressor cells (MDSCs), and T cell exhaustion, contributing to immune tolerance. CONCLUSION: These results indicate that DHX37 can serve as a prognostic biomarker in LIHC and LUAD while having an important role in immune tolerance by activating the function of Tregs, MDSC, and T cell exhaustion.
Sujet(s)
Adénocarcinome pulmonaire/mortalité , Marqueurs biologiques tumoraux/métabolisme , Carcinome hépatocellulaire/mortalité , Tumeurs du foie/mortalité , Tumeurs du poumon/mortalité , RNA helicases/métabolisme , Adénocarcinome pulmonaire/génétique , Adénocarcinome pulmonaire/immunologie , Adénocarcinome pulmonaire/anatomopathologie , Marqueurs biologiques tumoraux/analyse , Carcinome hépatocellulaire/génétique , Carcinome hépatocellulaire/immunologie , Carcinome hépatocellulaire/anatomopathologie , Jeux de données comme sujet , Femelle , Analyse de profil d'expression de gènes , Régulation de l'expression des gènes tumoraux/immunologie , Humains , Estimation de Kaplan-Meier , Tumeurs du foie/génétique , Tumeurs du foie/immunologie , Tumeurs du foie/anatomopathologie , Tumeurs du poumon/génétique , Tumeurs du poumon/immunologie , Tumeurs du poumon/anatomopathologie , Lymphocytes TIL/immunologie , Mâle , Cellules myéloïdes suppressives/immunologie , Pronostic , RNA helicases/analyse , Transduction du signal/génétique , Transduction du signal/immunologie , Lymphocytes T régulateurs/immunologie , Microenvironnement tumoral/génétique , Microenvironnement tumoral/immunologieRÉSUMÉ
Despite the functions of anti-PD-1 antibodies as immune checkpoint regulators, less than 30% of patients exhibit durable therapeutic responses to anti-PD-1 antibodies. Studies have shown that insufficient infiltration of immune cells might limit the outcome of anti-PD-1 therapy. Therefore, we synthesized an immune cell-recruiting liposomal system (FN-nps) to improve this therapeutic strategy. The FN-nps could generate cell debris and expose heat shock protein 70, which could recruit immune cells to tumor sites to assist in anti-PD-1 treatment. In vivo experiments revealed that the FN-nps could assist in anti-PD-1 therapy by increasing the number of lymphocytes in the peripheral blood and tumor site by generating tumor antigens, and this effect was accompanied by an increase in cytokine expression. The number of CTLs increased and mRNA expression levels of cytokines were regulated when the FN-nps were combined with anti-PD-1 therapy. The revealed properties of the liposomal system make it highly promising for assisting in anti-PD-1 antibody immunotherapy in different cancers.
Sujet(s)
Anticorps monoclonaux/métabolisme , Liposomes/composition chimique , Récepteur-1 de mort cellulaire programmée/immunologie , Animaux , Anticorps monoclonaux/composition chimique , Anticorps monoclonaux/usage thérapeutique , Lignée cellulaire tumorale , Survie cellulaire/effets des médicaments et des substances chimiques , Cytokines/sang , Femelle , Protéines du choc thermique HSP72/métabolisme , Humains , Souris , Souris de lignée BALB C , Microscopie de fluorescence , Nanoparticules/composition chimique , Nanoparticules/métabolisme , Nanoparticules/toxicité , Tumeurs/imagerie diagnostique , Tumeurs/traitement médicamenteux , Tumeurs/mortalité , Taux de survie , Lymphocytes T cytotoxiques/cytologie , Lymphocytes T cytotoxiques/immunologie , Distribution tissulaire , Transplantation hétérologue , ÉchographieRÉSUMÉ
The aim of this study was to analyze the features of non-mass breast lesions (NMLs) on B-mode ultrasound (US), color Doppler US, strain elastography (SE) and contrast-enhanced ultrasound (CEUS) and to develop a multimode ultrasonic method for NML differentiation. Seventy-one NMLs were included in this retrospective study. Binary logistic regression was used to identify the independent risk factors. Pathology results were used as the standard criterion. Microcalcification on US, high stiffness on SE and hyper-enhanced intensity on CEUS were identified as features correlated with malignancy. A multimode method to evaluate NMLs based on the logistic regression was developed. The sensitivity and specificity for US, US + Doppler, US + SE, US + CEUS and the multimode method were 100% and 29%, 92.5% and 41.9%, 97.5% and 58.1%, 90.0% and 58.1% and 95.0% and 77.4%, respectively. The accuracy of these methods was 69.0%, 70.4%, 80.2%, 76.1% and 87.3%, respectively. The multimode ultrasonic method is simple and exhibited high diagnostic performance, which might be helpful for predicting the potential malignancy of NMLs.
Sujet(s)
Tumeurs du sein/imagerie diagnostique , Imagerie d'élasticité tissulaire/méthodes , Imagerie multimodale/méthodes , Échographie-doppler couleur/méthodes , Échographie mammaire/méthodes , Adulte , Sujet âgé , Région mammaire/imagerie diagnostique , Produits de contraste , Diagnostic différentiel , Femelle , Humains , Amélioration d'image/méthodes , Adulte d'âge moyen , Études rétrospectives , Sensibilité et spécificité , Jeune adulteRÉSUMÉ
OBJECTIVES: To compare the diagnostic efficacies of B-mode ultrasound (US), strain elastography (SE), contrast-enhanced ultrasound (CEUS) and the combination of these modalities for breast lesions <1 cm in size. METHODS: Between January 2013 and October 2015, 203 inpatients with 209 sub-centimetre breast lesions categorised as BI-RADS-US (Breast Imaging Reporting and Data System for Ultrasound) 3-5 were included. US, SE and CEUS were performed to evaluate each lesion. The diagnostic performances of different ultrasonic modalities were compared. The diagnostic efficacies of BI-RADS-US and our re-rating systems were also compared. The pathology findings were used as the reference standard. RESULTS: The specificities of US, SE and CEUS for tumour differentiation were 17.4 %, 56.2 % and 86.0 %, respectively (P < 0.05); and the sensitivities were 100 %, 93.2 % and 93.2 % for US, SE and CEUS, respectively (P < 0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.867 for original BI-RADS-US, 0.882 for BI-RADS-US combined with only SE, 0.953 for BI-RADS-US combined with only CEUS and 0.924 for BI-RADS-US combined with both SE and CEUS. The best combination was BI-RADS-US combined with only CEUS. CONCLUSIONS: Evaluating sub-centimetre breast lesions with SE and CEUS could increase the diagnostic specificity while retaining high sensitivity compared with B-mode ultrasound. KEY POINTS: ⢠Evaluating breast lesions with SE and CEUS could increase the diagnostic specificity ⢠SE and CEUS offer alternatives to biopsy and possibly allow shorter-interval follow-ups ⢠BI-RADS-US combined with CEUS exhibited the best diagnostic performance.
Sujet(s)
Tumeurs du sein/imagerie diagnostique , Imagerie d'élasticité tissulaire/méthodes , Échographie mammaire/méthodes , Adolescent , Adulte , Sujet âgé , Aire sous la courbe , Biopsie , Région mammaire/imagerie diagnostique , Chine , Produits de contraste , Imagerie d'élasticité tissulaire/normes , Femelle , Humains , Adulte d'âge moyen , Imagerie multimodale/méthodes , Imagerie multimodale/normes , Courbe ROC , Sensibilité et spécificité , Échographie mammaire/normes , Jeune adulteRÉSUMÉ
The aim of the study was to develop a scoring model incorporating the Breast Imaging Reporting and Data System (BI-RADS) and the contrast-enhanced ultrasound (CEUS) scoring system to differentiate between malignant and benign breast lesions. A total of 524 solid breast masses in 490 consecutive patients were evaluated with conventional US and CEUS in this prospective study. Each lesion was scored according to BI-RADS, CEUS, and CEUS-rerated BI-RADS. The diagnostic specificity, sensitivity and accuracy of BI-RADS were 77.9%, 88.9% and 84.0%, respectively, and the area under the receiver operating characteristic curve was 0.834. The corresponding values for rerated BI-RADS were 82.1%, 96.9%, 90.3% and 0.895. The area under the receiver operating characteristic curve of BI-RADS alone was significantly smaller than that of CEUS and the rerated BI-RADS (p = 0.008 compared with CEUS, p = 0.002 compared with rerated BI-RADS). This study indicates that rerating BI-RADS with the CEUS scoring system improves its diagnostic accuracy.
Sujet(s)
Tumeurs du sein/imagerie diagnostique , Produits de contraste , Amélioration d'image/méthodes , Systèmes d'information de radiologie , Échographie mammaire/méthodes , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Région mammaire/imagerie diagnostique , Chine , Diagnostic différentiel , Femelle , Humains , Adulte d'âge moyen , Études prospectives , Reproductibilité des résultats , Sensibilité et spécificité , Jeune adulteRÉSUMÉ
OBJECTIVE: To evaluate the diagnostic performance of superb microvascular imaging (SMI) in breast lesions, comparing with contrast-enhanced ultrasonographic microvascular imaging (MVI). METHODS: From April to November 2015, 132 patients (with 132 breast lesions) were enrolled in the retrospective study. All lesions were evaluated with colour Doppler flow imaging (CDFI), colour SMI (cSMI), monochrome SMI (mSMI) and contrast-enhanced ultrasonographic MVI. Receiver-operating characteristic curve analysis was performed to compare the diagnostic performance of SMI and MVI for discrimination between benign and malignant breast lesions. RESULTS: Histological analysis showed 58 malignant and 74 benign lesions. mSMI was more sensitive in detecting blood flow signals in breast lesions than CDFI (p < 0.001) and cSMI (p < 0.001). Differences of vessels inside breast lesions and morphologic features of vessels between benign and malignant lesions were statistically significant on mSMI (p < 0.001). Using root hair-like and crab claw-like patterns as the criteria for malignant lesions, the sensitivity, specificity and accuracy for differentiation based on the microvascular architecture patterns were 77.6, 90.5 and 84.8% for mSMI and 89.6, 87.8 and 88.6% for MVI. Areas under curve of mSMI and MVI were not significantly different (p = 0.129). CONCLUSION: mSMI can increase blood flow detection and depict the microvascular architecture of breast lesions. The diagnostic performance of mSMI was not significantly different from MVI. SMI has potential in the differential diagnosis of breast lesions. ADVANCES IN KNOWLEDGE: mSMI is a non-invasive technique for vascularity evaluation of breast tumours and it is beneficial for breast tumour differentiation.
Sujet(s)
Tumeurs du sein/vascularisation , Tumeurs du sein/imagerie diagnostique , Microvaisseaux/imagerie diagnostique , Néovascularisation pathologique/imagerie diagnostique , Échographie mammaire/méthodes , Adolescent , Adulte , Sujet âgé , Produits de contraste , Diagnostic différentiel , Femelle , Humains , Amélioration d'image/méthodes , Interprétation d'images assistée par ordinateur/méthodes , Adulte d'âge moyen , Débit sanguin régional , Reproductibilité des résultats , Études rétrospectives , Sensibilité et spécificité , Échographie-doppler couleur/méthodesRÉSUMÉ
BACKGROUND: A high neutrophil-to-lymphocyte ratio (NLR) may be related to increased mortality in patients with lung, colorectal, stomach, liver, and pancreatic cancer. To date, the utility of NLR to predict the response to neoadjuvant chemotherapy (NAC) has not been studied. The aim of our study was to determine whether the NLR is a predictor of response to NAC and to investigate the prognostic impact of the NLR on relapse-free survival (RFS) and breast cancer-specific survival (BCSS) in patients with breast cancer who received NAC. METHODS: We retrospectively studied patients who received NAC and subsequent surgical therapy for stage II-III invasive breast carcinoma at Sun Yat-sen Memorial Hospital between 2001 and 2010. The correlation of NLR with the pathological complete response (pCR) rate of invasive breast cancer to NAC was analyzed. Survival analysis was used to evaluate the predictive value of NLR. RESULTS: A total of 215 patients were eligible for analysis. The pCR rate in patients with lower pretreatment NLR (NLR < 2.06) was higher than those with higher NLR (NLR ≥ 2.06) (24.5 % vs.14.3 %, p < 0.05). Those patients with higher pretreatment NLR (NLR ≥ 2.1) had more advanced stages of cancer and higher disease-specific mortality. Through a multivariate analysis including all known predictive clinicopathologic factors, NLR ≥ 2.1 was a significant independent parameter affecting RFS (HR: 1.57, 95 % CI: 1.05-3.57, p < 0.05) and BCSS (HR: 2.21, 95 % CI: 1.01-4.39, p < 0.05). Patients with higher NLR (NLR ≥ 2.1) before treatment showed significantly lower relapse-free survival rate and breast cancer-specific survival rate than those with lower NLR (NLR <2.1) (log-rank p = 0.0242 and 0.186, respectively). CONCLUSIONS: Pretreatment NLR < 2.06 is associated with pCR rate, suggesting that NLR may be an important factor predicting the response to NAC in breast cancer patients. NLR is an independent predictor of RFS and BCSS in breast cancer patients with NLR ≥ 2.1 who receive NAC. We suggest prospective studies to evaluate NLR as a simple prognostic test for breast cancer.
Sujet(s)
Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Tumeurs du sein/anatomopathologie , Carcinome canalaire du sein/anatomopathologie , Adulte , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/immunologie , Carboplatine/administration et posologie , Carcinome canalaire du sein/traitement médicamenteux , Carcinome canalaire du sein/mortalité , Traitement médicamenteux adjuvant , Cyclophosphamide/administration et posologie , Survie sans rechute , Docetaxel , Épirubicine/administration et posologie , Femelle , Humains , Estimation de Kaplan-Meier , Numération des lymphocytes , Lymphocytes/anatomopathologie , Analyse multifactorielle , Traitement néoadjuvant , Granulocytes neutrophiles/anatomopathologie , Pronostic , Modèles des risques proportionnels , Courbe ROC , Études rétrospectives , Taxoïdes/administration et posologie , Trastuzumab/administration et posologie , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: There is an unmet need for specific and sensitive imaging techniques to assess the efficacy of breast cancer therapy, particularly Her-2-expressing cancers. Ultrasonic microbubbles are being developed for use as diagnostic and therapeutic tools. However, nanobubbles circulate longer, are smaller, and diffuse into extravascular tissue to specifically bind target molecules. Here, we characterize a novel Herceptin-conjugated nanobubble for use against Her-2-expressing tumors. METHODS: Phospholipid-shelled nanobubbles conjugated with Herceptin (NBs-Her) were fabricated using a thin-film hydration method and characterized in vitro in breast cancer cell lines and in vivo in a mouse model. RESULTS: The average size of the unconjugated nanobubbles (NBs-Blank) and NBs-Her was 447.1 ± 18.4 and 613.0 ± 25.4 nm, respectively. In cell culture, the NBs-Her adhered to Her-2-positive cells significantly better than to Her-2-negative cells (p < 0.05). In vivo, the peak intensity and the half-time to washout of the NBs-Her were significantly greater than those of the NBs-Blank (p < 0.05). In addition, contrast-enhanced ultrasound imaging quality was improved through the use of the NBs-Her. The nanobubbles were able to penetrate into tumor tissue to allow extravascular imaging, but did not penetrate normal skeletal muscle. CONCLUSIONS: The Herceptin-conjugated nanobubble had many properties that made it useful for in vivo imaging, including longer circulation time and better tumor selectivity. This platform may be able to provide targeted delivery of therapeutic drugs or genes.
Sujet(s)
Tumeurs du sein/imagerie diagnostique , Produits de contraste/composition chimique , Produits de contraste/pharmacocinétique , Récepteur ErbB-2/métabolisme , Trastuzumab/administration et posologie , Animaux , Tumeurs du sein/métabolisme , Lignée cellulaire tumorale , Femelle , Humains , Souris nude , Microbulles , Nanostructures/composition chimique , Phospholipides/composition chimique , Trastuzumab/composition chimique , Trastuzumab/pharmacocinétique , Échographie mammaire , Tests d'activité antitumorale sur modèle de xénogreffeRÉSUMÉ
This study aims to investigate the relation of syntactic and discourse skills to morphological skills, rapid naming, and working memory in Chinese adolescent readers with dyslexia and to examine their cognitive-linguistic profiles. Fifty-two dyslexic readers (mean age, 13;42) from grade 7 to 9 in Hong Kong high schools were compared with 52 typically developing readers of the same chronological age (mean age, 13;30) in the measures of word reading, 1-min word reading, reading comprehension, morpheme discrimination, morpheme production, morphosyntactic knowledge, sentence order knowledge, digit rapid naming, letter rapid naming, backward digit span, and non-word repetition. Results showed that dyslexic readers performed significantly worse than their peers on all the cognitive-linguistic tasks. Analyses of individual performance also revealed that over half of the dyslexic readers exhibited deficits in syntactic and discourse skills. Moreover, syntactic skills, morphological skills, and rapid naming best distinguished dyslexic from non-dyslexic readers. Findings underscore the significance of syntactic and discourse skills for understanding reading impairment in Chinese adolescent readers.
Sujet(s)
Cognition/physiologie , Dyslexie/physiopathologie , Langage , Mémoire à court terme/physiologie , Lecture , Adolescent , Compréhension/physiologie , Femelle , Hong Kong , Humains , Tests du langage/statistiques et données numériques , Linguistique/méthodes , Mâle , PhonétiqueRÉSUMÉ
OBJECTIVES: Although many studies about breast contrast-enhanced ultrasound had been conducted, clear diagnostic criteria for evaluating enhancement patterns are still lacking. This study aims to identify significant indicators for breast contrast-enhanced ultrasound and to establish an initial scoring system. MATERIALS AND METHODS: Totally 839 patients were included in the study. This study was divided into two parts. 364 patients were included in part 1 while 475 in part 2. Conventional ultrasound and contrast-enhanced ultrasound were used to examine each lesion. Only the cases in part 2 were also examined by elastography. In part 1, Logistic regression analysis was performed to predict significant variables. A 5-point scoring system was developed based on the results. In part 2, the scoring system was used to evaluate all the breast lesions. To evaluate the diagnostic efficacy of the new scoring system, it was compared with the system established for elastography and conventional ultrasound (BI-RADS). RESULTS: Three independent variables, namely, lesion scope, margin, and shape were selected in the final step of the logistic regression analysis in part 1. In part 2, the area under the ROC (receiver operating characteristic) curve for the contrast-enhanced scoring system was 0.912. The difference in the diagnostic capabilities of the contrast-enhanced scoring system and elastography was not statistically significant (Pâ=â0.17). The difference in the diagnostic capabilities of the contrast-enhanced scoring system and BI-RADS was statistically significant (P<0.001). CONCLUSIONS: The contrast-enhanced patterns of benign and malignant breast tumors are different. The application of a 5-point scoring system for contrast-enhanced ultrasound is clinically promising.