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1.
Breast ; 76: 103762, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38924994

RESUMEN

BACKGROUND: Male breast cancer (MBC) is a rare disease. Although several large-scale studies have investigated MBC patients in other countries, the features of MBC patients in China have not been fully explored. This study aims to explore the features of Chinese MBC patients comprehensively. METHODS: We retrospectively collected data of MBC patients from 36 centers in China. Overall survival (OS) was evaluated by the Kaplan-Meier method, log-rank test, and Cox regression analyses. Multivariate Cox analyses were used to identify independent prognostic factors of the patients. RESULTS: In total, 1119 patients were included. The mean age at diagnosis was 60.9 years, and a significant extension over time was observed (P < 0.001). The majority of the patients (89.1 %) received mastectomy. Sentinel lymph node biopsy was performed in 7.8 % of the patients diagnosed in 2009 or earlier, and this percentage increased significantly to 38.8 % in 2020 or later (P < 0.001). The five-year OS rate for the population was 85.5 % [95 % confidence interval (CI), 82.8 %-88.4 %]. Multivariate Cox analysis identified taxane-based [T-based, hazard ratio (HR) = 0.32, 95 % CI, 0.13 to 0.78, P = 0.012] and anthracycline plus taxane-based (A + T-based, HR = 0.47, 95 % CI, 0.23 to 0.96, P = 0.037) regimens as independent protective factors for OS. However, the anthracycline-based regimen showed no significance in outcome (P = 0.175). CONCLUSION: As the most extensive MBC study in China, we described the characteristics, treatment and prognosis of Chinese MBC population comprehensively. T-based and A + T-based regimens were protective factors for OS in these patients. More research is required for this population.


Asunto(s)
Neoplasias de la Mama Masculina , Mastectomía , Biopsia del Ganglio Linfático Centinela , Humanos , Neoplasias de la Mama Masculina/patología , Neoplasias de la Mama Masculina/mortalidad , Neoplasias de la Mama Masculina/terapia , Neoplasias de la Mama Masculina/epidemiología , Masculino , Persona de Mediana Edad , China/epidemiología , Estudios Retrospectivos , Mastectomía/estadística & datos numéricos , Anciano , Biopsia del Ganglio Linfático Centinela/estadística & datos numéricos , Adulto , Pronóstico , Modelos de Riesgos Proporcionales , Estimación de Kaplan-Meier , Taxoides/uso terapéutico , Tasa de Supervivencia , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Antraciclinas/uso terapéutico , Anciano de 80 o más Años
2.
Clin Transl Med ; 14(5): e1681, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38725048

RESUMEN

BACKGROUND: We explored the potential novel anticancer mechanisms of 25-hydroxyvitamin D (25(OH)D), a vitamin D metabolite with antitumour effects in breast cancer. It is stable in serum and is used to assess vitamin D levels in clinical practice. Transfer RNA-derived small RNAs are small noncoding RNAs that generate various distinct biological functions, but more research is needed on their role in breast cancer. METHODS: Small RNA microarrays were used to explore the novel regulatory mechanism of 25(OH)D. High-throughput RNA-sequencing technology was used to detect transcriptome changes after 25(OH)D treatment and tRF-1-Ser knockdown. RNA pull-down and high-performance liquid chromatography-mass spectrometry/mass spectrometry were used to explore the proteins bound to tRF-1-Ser. In vitro and in vivo functional experiments were conducted to assess the influence of 25(OH)D and tRF-1-Ser on breast cancer. Semi-quantitative PCR was performed to detect alternative splicing events. Western blot assay and qPCR were used to assess protein and mRNA expression. RESULTS: The expression of tRF-1-Ser is negatively regulated by 25(OH)D. In our breast cancer (BRCA) clinical samples, we found that the expression of tRF-1-Ser was higher in cancer tissues than in paired normal tissues, and was significantly associated with tumour invasion. Moreover, tRF-1-Ser inhibits the function of MBNL1 by hindering its nuclear translocation. Functional experiments and transcriptome data revealed that the downregulation of tRF-1-Ser plays a vital role in the anticancer effect of 25(OH)D. CONCLUSIONS: In brief, our research revealed a novel anticancer mechanism of 25(OH)D, unveiled the vital function of tRF-1-Ser in BRCA progression, and suggested that tRF-1-Ser could emerge as a new therapeutic target for BRCA.


Asunto(s)
Neoplasias de la Mama , Proliferación Celular , Proteínas de Unión al ARN , Vitamina D , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Vitamina D/metabolismo , Vitamina D/análogos & derivados , Vitamina D/farmacología , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Proliferación Celular/genética , Ratones , Animales
3.
J Med Chem ; 67(11): 8667-8692, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38651495

RESUMEN

The targeting of cancer cell intrinsic metabolism has emerged as a promising strategy for antitumor intervention. In the study, we identified the first-in-class small molecules that effectively inhibit both mutant isocitrate dehydrogenase 1 (mIDH1) and nicotinamide phosphoribosyltransferase (NAMPT), two crucial targets in cancer metabolism, through structure-based drug design. Notably, compound 23h exhibits excellent and balanced inhibitory activities against both mIDH1 (IC50 = 14.93 nM) and NAMPT (IC50 = 12.56 nM), leading to significant suppression of IDH1-mutated glioma cell (U87 MG-IDH1R132H) proliferation. Significantly, compound 23h has the ability to cross the blood-brain barrier (B/P ratio, 0.76) and demonstrates remarkable in vivo antitumor efficacy (20 mg/kg) in the U87 MG-IDH1R132H orthotopic transplantation mouse models without any notable toxicity. This proof-of-concept investigation substantiates the viability of discovering small molecules that concurrently target mIDH1 and NAMPT, providing valuable leads for the treatment of glioma and an efficient approach for the discovery of multitarget antitumor drugs.


Asunto(s)
Antineoplásicos , Proliferación Celular , Citocinas , Glioma , Isocitrato Deshidrogenasa , Nicotinamida Fosforribosiltransferasa , Nicotinamida Fosforribosiltransferasa/antagonistas & inhibidores , Nicotinamida Fosforribosiltransferasa/metabolismo , Isocitrato Deshidrogenasa/antagonistas & inhibidores , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , Glioma/tratamiento farmacológico , Glioma/patología , Animales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Antineoplásicos/síntesis química , Ratones , Citocinas/metabolismo , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Mutación , Descubrimiento de Drogas , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Relación Estructura-Actividad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/uso terapéutico , Inhibidores Enzimáticos/síntesis química , Ratones Desnudos
4.
Sensors (Basel) ; 24(7)2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38610244

RESUMEN

Acoustic imaging technology has the advantages of non-contact and intuitive positioning. It is suitable for the rapid positioning of defects such as the mechanical loosening, discharge, and DC bias of power equipment. However, the existing research lacks the optimization design of microphone array topology. The acoustic frequency domain characteristics of typical power equipment are elaborately sorted out. After that, the cut-off frequencies of acoustic imaging instruments are determined, to meet the needs of the full bandwidth test requirements. Through a simulation calculation, the circular array is demonstrated to be the optimal shape. And the design parameters affect the imaging performance of the array to varying degrees, indicating that it is difficult to obtain the optimal array topology by an exhaustive method. Aimed at the complex working conditions of power equipment, a topology optimization design method of an acoustic imaging array for power equipment is proposed, and the global optimal solution of microphone array topology is obtained. Compared with the original array, the imaging performance of the improved LF and HF array is promoted by 54% and 49%, respectively. Combined with the simulation analysis and laboratory test, it is verified that the improved array can not only accurately locate the single sound source but also accurately identify the main sound source from the interference of the contiguous sound source.

5.
Br J Radiol ; 97(1153): 228-236, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38263817

RESUMEN

OBJECTIVE: To establish a nomogram for predicting the pathologic complete response (pCR) in breast cancer (BC) patients after NAC by applying magnetic resonance imaging (MRI) and ultrasound (US). METHODS: A total of 607 LABC women who underwent NAC before surgery between January 2016 and June 2022 were retrospectively enrolled, and then were randomly divided into the training (n = 425) and test set (n = 182) with the ratio of 7:3. MRI and US variables were collected before and after NAC, as well as the clinicopathologic features. Univariate and multivariate logistic regression analyses were applied to confirm the potentially associated predictors of pCR. Finally, a nomogram was developed in the training set with its performance evaluated by the area under the receiver operating characteristics curve (ROC) and validated in the test set. RESULTS: Of the 607 patients, 108 (25.4%) achieved pCR. Hormone receptor negativity (odds ratio [OR], 0.3; P < .001), human epidermal growth factor receptor 2 positivity (OR, 2.7; P = .001), small tumour size at post-NAC US (OR, 1.0; P = .031), tumour size reduction ≥50% at MRI (OR, 9.8; P < .001), absence of enhancement in the tumour bed at post-NAC MRI (OR, 8.1; P = .003), and the increase of ADC value after NAC (OR, 0.3; P = .035) were all significantly associated with pCR. Incorporating the above variables, the nomogram showed a satisfactory performance with an AUC of 0.884. CONCLUSION: A nomogram including clinicopathologic variables and MRI and US characteristics shows preferable performance in predicting pCR. ADVANCES IN KNOWLEDGE: A nomogram incorporating MRI and US with clinicopathologic variables was developed to provide a brief and concise approach in predicting pCR to assist clinicians in making treatment decisions early.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Imagen por Resonancia Magnética , Terapia Neoadyuvante , Nomogramas , Estudios Retrospectivos
6.
Bioorg Med Chem ; 99: 117595, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38244254

RESUMEN

Nicotinamide phosphoribosyltransferase (NAMPT) is a key rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD+) salvage pathway, primarily catalyzing the synthesis of nicotinamide mononucleotide (NMN) from nicotinamide (NAM), phosphoribosyl pyrophosphate (PRPP), and adenosine triphosphate (ATP). Metabolic diseases, aging-related diseases, inflammation, and cancers can lead to abnormal expression levels of NAMPT due to the pivotal role of NAD+ in redox metabolism, aging, the immune system, and DNA repair. In addition, NAMPT can be secreted by cells as a cytokine that binds to cell membrane receptors to regulate intracellular signaling pathways. Furthermore, NAMPT is able to reduce therapeutic efficacy by enhancing acquired resistance to chemotherapeutic agents. Recently, a few novel activators and inhibitors of NAMPT for neuroprotection and anti-tumor have been reported, respectively. However, NAMPT activators are still in preclinical studies, and only five NAMPT inhibitors have entered the clinical stage, unfortunately, three of which were terminated or withdrawn due to safety concerns. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), antibody-drug conjugate (ADC), and dual-targeted inhibitors also provide new directions for the development of NAMPT inhibitors. In this perspective, we mainly discuss the structure, biological function, and role of NAMPT in diseases and the currently discovered activators and inhibitors. It is our hope that this work will provide some guidance for the future design and optimization of NAMPT activators and inhibitors.


Asunto(s)
NAD , Neoplasias , Humanos , NAD/metabolismo , Nicotinamida Fosforribosiltransferasa , Citocinas/metabolismo , Niacinamida , Descubrimiento de Drogas , Neoplasias/tratamiento farmacológico
7.
Molecules ; 28(22)2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-38005204

RESUMEN

In this study, we not only optimized and improved the synthesis process of levobupivacaine hydrochloride (21) but also conducted a comprehensive exploration of critical industrial-scale production details, and a novel high-performance liquid chromatography (HPLC) analysis method was developed. Starting with the readily available and cost-effective (R,S)-N-(2,6-dimethylphenyl)piperidine-2-carboxamide (28) as the initial material and utilizing l-(-)-dibenzoyl tartaric acid (29) for chiral separation, and then through substitution and a salting reaction, levobupivacaine hydrochloride (21) was obtained with high purity (chemical purity of 99.90% and enantiomeric excess (ee) values of 99.30%). The total yield of the three steps was 45%. Structures of intermediates and the final product were confirmed using nuclear magnetic resonance (NMR) (1H NMR, 13C NMR), mass spectrometry (MS), and elemental analysis. The crystal structure of the final product was determined through differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). Furthermore, we evaluated the risk of the substitution reaction using a reaction calorimeter and accelerating rate calorimetry (ARC). This process offers the advantages of simple operation, greenness, safety, controllable quality, and cost-effectiveness. It provides reliable technical support for the industrial-scale production of levobupivacaine hydrochloride (21), which is of significant importance in meeting clinical demands. Pilot-scale production has already been successfully completed by China National Medicines Guorui Pharmaceutical Co., Ltd., with a production scale of 20 kg.

8.
Nanomedicine ; 54: 102707, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37717927

RESUMEN

PURPOSE: There are four kinds of taxanes: solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel. This study aims to retrospectively evaluate the efficacy of different taxanes on neoadjuvant systemic treatment (NST) in breast cancer. METHODS: Patients who were diagnosed with breast cancer and had received integral NST from August 2013 to April 2022 were enrolled. The efficacy was divided into total pathological complete response (total-pCR), breast pathological complete response (breast-pCR), and axillary pathological complete response (axillary-pCR) for in-depth analysis and discussion. RESULTS: The choice of taxane was an independent risk factor for total-pCR and breast-pCR rates. The highest total-pCR and breast-pCR rates were found in the Nab-P group. The difference was not significant among all the taxanes in the axillary-pCR rate. CONCLUSION: Nab-P significantly improved the total-pCR and breast-pCR rates. It should be the first choice among taxanes in NST for breast cancer.


Asunto(s)
Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Docetaxel/uso terapéutico , Paclitaxel Unido a Albúmina/uso terapéutico , Terapia Neoadyuvante , Estudios Retrospectivos , Paclitaxel/uso terapéutico , Albúminas , Taxoides/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica
9.
Ren Fail ; 45(1): 2210227, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37170583

RESUMEN

INTRODUCTION: Blood bone metabolic biomarkers are noninvasive indices for evaluating metabolic bone diseases. We investigated the relationships between blood bone metabolic biomarkers and anemia in chronic kidney disease (CKD) patients and analyzed the effects of parathyroidectomy (PTX) on the above indices. METHODS: In this cross-sectional study, 100 healthy controls and 239 CKD patients, including 46 secondary hyperparathyroidism (SHPT) patients with PTX, were enrolled. Moreover, a prospective study was conducted in which 28 PTX patients were followed up. The degree of anemia was classified as mild, moderate, or severe based on the tertiles of hemoglobin (Hb) levels of the anemic CKD patients, with cutoff values of 83 g/L and 102 g/L. Bone metabolic biomarkers, including calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF23), and α-klotho, were tested. RESULTS: The mean estimated glomerular filtration rate (eGFR) in CKD patients was 25.7 ± 36.0 ml/min/1.73 m2, and 84.10% of CKD patients had anemia. The baseline Hb levels in the mild, moderate, and severe anemia subgroups were 110.86 ± 5.99 g/L, 92.71 ± 5.96 g/L, and 67.38 ± 10.56 g/L, respectively. CKD patients had higher adjusted Ca, P, alkaline phosphatase (ALP), iPTH, and FGF23 levels and lower α-klotho levels than controls. Baseline adjusted Ca, P, iPTH, and α-klotho levels were associated with Hb levels in CKD patients. Blood adjusted Ca, P, and iPTH levels were correlated with anemia severity. After PTX (median interval: 6.88 months), anemia and high blood adjusted Ca, P, iPTH, and FGF23 levels were ameliorated, while α-klotho levels were increased. CONCLUSIONS: Blood adjusted Ca, P, iPTH, and α-klotho levels were correlated with Hb levels in CKD patients. Correction of bone metabolic disorders may be a therapeutic strategy for anemia treatment.


Asunto(s)
Anemia , Enfermedades Óseas Metabólicas , Insuficiencia Renal Crónica , Humanos , Estudios Transversales , Estudios Prospectivos , Insuficiencia Renal Crónica/complicaciones , Hormona Paratiroidea , Calcio , Anemia/complicaciones , Enfermedades Óseas Metabólicas/etiología , Biomarcadores
10.
Eur J Med Chem ; 250: 115232, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36863225

RESUMEN

Nuclear receptor-binding SET domain 2 (NSD2) is a histone lysine methyltransferase (HKMTase), which is mainly responsible for the di-methylation of lysine residues on histones, which are involved in the regulation of various biological pathways. The amplification, mutation, translocation, or overexpression of NSD2 can be linked to various diseases. NSD2 has been identified as a promising drug target for cancer therapy. However, relatively few inhibitors have been discovered and this field still needs further exploration. This review provides a detailed summary of the biological studies related to NSD2 and the current progress of inhibitors, research, and describes the challenges in the development of NSD2 inhibitors, including SET (su(var), enhancer-of-zeste, trithorax) domain inhibitors and PWWP1 (proline-tryptophan-tryptophan-proline 1) domain inhibitors. Through analysis and discussion of the NSD2-related crystal complexes and the biological evaluation of related small molecules, we hope to provide insights for future drug design and optimization methods that will stimulate the development of novel NSD2 inhibitors.


Asunto(s)
Dominios PR-SET , Proteínas Represoras , Proteínas Represoras/metabolismo , Histonas/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo
11.
Nanomedicine ; 49: 102666, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36889422

RESUMEN

This study aimed to compare the efficacy of neoadjuvant systemic therapy (NST) with solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel in human epidermal growth factor receptor 2 (HER2)-low-positive and HER2-zero breast cancers. A total of 430 patients receiving 2-weekly dose-dense epirubicin and cyclophosphamide (EC) followed by 2-weekly paclitaxel (Sb-P, Lps-P, or Nab-P), or 3-weekly EC followed by 3-weekly docetaxel for NST were enrolled in the study. In HER2-low-positive patients, the pathological complete response (pCR) rate in Nab-P group was significantly higher than that in the other three paclitaxel groups (2.8 % in Sb-P group, 4.7 % in Lps-P group, 23.2 % in Nab-P group and 3.2 % in docetaxel group, p < 0.001). In HER2-zero patients, the pCR rate did not differ significantly among the four paclitaxel groups (p = 0.278). The NST regimen containing Nab-P could be considered a promising treatment option in HER2-low-positive breast cancer.


Asunto(s)
Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Neoplasias de la Mama/patología , Paclitaxel Unido a Albúmina/uso terapéutico , Terapia Neoadyuvante , Docetaxel/uso terapéutico , Lipopolisacáridos , Ciclofosfamida/uso terapéutico , Epirrubicina/uso terapéutico , Paclitaxel/uso terapéutico , Albúminas , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento
12.
Front Oncol ; 13: 910869, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36814820

RESUMEN

Neoadjuvant systemic therapy (NST) is widely applied in breast cancer treatment, but individuals respond differently to the same NST regimen. It is unclear which patients should adjust their NST regimen and what such an adjustment should be, especially for patients with radiologically partial response (PR). This study aimed to identify a quantitative efficacy evaluation index to evaluate the therapeutic effect of NST. 164 patients were enrolled in this study received four cycles of epirubicin and cyclophosphamide (EC), followed by four cycles of taxanes with trastuzumab [T(H)], if needed. Of patients with a volume change rate of EC treatment (δV1) below 0.80, more than half benefited from subsequent T(H) treatment compared with EC treatment. Importantly, for δV1 of 0.80 and higher, patients' subsequent T(H) treatment was not as efficient as previous EC treatment and they have a lower pathological complete response (pCR) rate. Across all patients, nanoparticle albumin-bound paclitaxel had a numerically higher pCR rate over other taxanes in patients with triple-negative breast cancer. This study showed that the volume change rate is better than the diameter change rate in monitoring the therapeutic effect of NST. Furthermore, δV1 is a good quantitative efficacy evaluation index to distinguish patients resistant to EC treatment and predict the pCR rate and guide the adjustment of individualized NST regimens.

13.
Cancer Med ; 12(8): 9363-9372, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36794698

RESUMEN

BACKGROUND: Patients who do not achieve a pathological complete response (pCR) after neoadjuvant systemic treatment (NST) have a significantly worse prognosis. A reliable predictor of prognosis is required to further subdivide non-pCR patients. To date, the prognostic role in terms of disease-free survival (DFS) between the terminal index of Ki-67 after surgery (Ki-67T ) and the combination of the baseline Ki-67 at biopsy before NST (Ki-67B ) and the percentage change in Ki-67 before and after NST (Ki-67C ) has not been compared. AIM: This study aimed to explore the most useful form or combination of Ki-67 that can provide prognostic information to non-pCR patients. PATIENTS AND METHODS: We retrospectively reviewed 499 patients who were diagnosed with inoperable breast cancer between August 2013 and December 2020 and received NST with anthracycline plus taxane. RESULTS: Among all the patients, 335 did not achieve pCR (with a follow-up period of ≥1 year). The median follow-up duration was 36 months. The optimal cutoff value of Ki-67C to predict a DFS was 30%. A significantly worse DFS was observed in patients with a low Ki-67C (p < 0.001). In addition, the exploratory subgroup analysis showed relatively good internal consistency. Ki-67C and Ki-67T were considered as independent risk factors for DFS (both p < 0.001). The forecasting model combining Ki-67B and Ki-67C showed a significantly higher area under the curve at years 3 and 5 than Ki-67T (p = 0.029 and p = 0.022, respectively). CONCLUSIONS: Ki-67C and Ki-67T were good independent predictors of DFS, whereas Ki-67B was a slightly inferior predictor. The combination of Ki-67B and Ki-67C is superior to Ki-67T for predicting DFS, especially at longer follow-ups. Regarding clinical application, this combination could be used as a novel indicator for predicting DFS to more clearly identify high-risk patients.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Pronóstico , Neoplasias de la Mama/patología , Antígeno Ki-67/análisis , Estudios Retrospectivos , Terapia Neoadyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad
14.
J Investig Med ; 71(4): 384-393, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36655808

RESUMEN

Previous studies have observed that human epidermal growth factor receptor 2 (HER2)-low-positive patients and HER2-zero patients have different prognoses. This study was conducted to investigate whether there are differences in clinicopathological characteristics and the response to neoadjuvant systemic therapy (NST) defined as systemic treatment prior to surgery between HER2-low-positive patients and HER2-zero patients. We retrospectively analyzed the data of patients with HER2-negative breast cancer who received NST at the First Affiliated Hospital of Nanjing Medical University from 2014 to 2021. There were 238 patients with HER2-low-positive status and 198 patients with HER2-zero status. The proportion of hormone receptor (HR)-positive patients in the HER2-low-positive group was significantly higher than that in the HER2-zero group (82.8% vs 52.0%, p < 0.001). The HER2-low-positive group had more patients with low Ki67 expression (23.9% vs 16.2%, p = 0.045), higher mastectomy rate (94.5% vs 88.9%, p = 0.031), and larger pathological tumor size (21.6 vs 17.8 mm, p = 0.028) than the HER2-zero group. However, no significant differences were found in pathologic complete response (pCR) rates between the two groups. We draw a conclusion that patients with HER2-low status and HER2-zero status were not found to have different pCR rates after NST, irrespective of HR status. However, differences were observed in some clinicopathological characteristics between the two groups.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Terapia Neoadyuvante , Estudios Retrospectivos , Mastectomía , Pronóstico
15.
Br J Clin Pharmacol ; 89(1): 372-379, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36001055

RESUMEN

AIMS: As one of the mainstays of breast cancer therapy, chemotherapy inevitably induces neutropenia. In this study, we explored the role of PEG-rhG-CSF (pegylated recombinant human granulocyte colony-stimulating factor) in the emergency treatment of chemotherapy-induced grades 3-4 neutropenia. METHODS: A total of 100 patients with breast cancer were randomized (1:1) into the study. Fifty patients randomized to the experimental group were treated with PEG-rhG-CSF after grades 3-4 neutropenia following the first cycle of chemotherapy, while 50 patients randomized to the control group received a daily injection of rhG-CSF (recombinant human granulocyte colony-stimulating factor). The primary endpoint was the recovery time of grades 3-4 neutropenia. RESULTS: Compared with patients in the control group, the mean ± SD recovery time of grades 3-4 neutropenia and febrile neutropenia (FN) was significantly shorter for patients in the experimental group (grades 3-4, P = .000; grade 4, P = .000; FN, P = .038). There is no significant difference in the incidence of FN for the two groups. In the experimental group, the duration of grades 3-4 neutropenia in patients aged <60 years and ≥60 years was 2.15 and 3.20 days, respectively (P = .037). Adverse events (AEs) of any grade were reported in 37 (75.5%) and 28 (59.6%) patients from the two groups, respectively. No grade ≥3 AEs were reported. CONCLUSION: This study supported that the PEG-rhG-CSF was more effective and convenient than rhG-CSF for treating grades 3-4 neutropenia and FN in patients with breast cancer and had manageable toxicity.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Neutropenia Febril , Neoplasias Pulmonares , Humanos , Femenino , Neoplasias Pulmonares/tratamiento farmacológico , Estudios Prospectivos , Polietilenglicoles , Neoplasias de la Mama/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Proteínas Recombinantes , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tratamiento de Urgencia , Antineoplásicos/efectos adversos , Neutropenia Febril/inducido químicamente
16.
Front Endocrinol (Lausanne) ; 13: 1042394, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36506067

RESUMEN

Background: Neoadjuvant systemic therapy (NST) could make some clinically node-positive (cN+) breast cancer patients achieve axillary pathologic complete response (pCR). This study aimed to identify the patients who are likely to achieve axillary pCR and help surgeons make surgical decisions on the axilla. Methods: The cN+ breast cancer patients who received NST from 2015 to 2021 at The First Affiliated Hospital of Nanjing Medical University were enrolled. Univariate and multivariate logistic regression analyses were performed, and a nomogram was constructed based on the results of multivariate logistic regression analysis to predict the probability of axillary pCR and validated. Results: The axillary pCR was achieved in 208 (38.7%) patients. Patients who had a higher radiological response rate of breast tumor (P = 0.039), smaller longest diameter of positive node after NST (P = 0.028), ER-negative status (P = 0.006), HER2-positive status (P = 0.048) and breast pCR (P < 0.001) were more likely to achieve axillary pCR. The nomogram had an area under the receiver operating characteristic curve (AUC) of 0.795 (95% CI: 0.747-0.843), and the calibration curve showed good agreement. Conclusion: A nomogram was constructed to predict the axillary pCR of cN+ patients receiving NST based on baseline and efficacy indicators to assist surgeons in making surgical decisions on the axilla.


Asunto(s)
Neoplasias de la Mama , Terapia Neoadyuvante , Humanos , Femenino , Terapia Neoadyuvante/métodos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Metástasis Linfática , Axila/patología , Nomogramas
17.
Front Oncol ; 12: 896431, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36568204

RESUMEN

Background: Adjuvant chemotherapy is a major adjuvant treatment modality for hormonal receptor (HR)-positive and HER2-negative early breast cancer, but only 2%-20% of patients derive practical benefits. How to balance its potential benefits and risks becomes a challenging clinical problem. The purpose of this study was to assess whether RecurIndex assay could serve as an aid for adjuvant chemotherapy decisions in Chinese patients with HR-positive HER2-negative early breast cancer. Methods: The tissue samples of pT1-2N0 HR-positive HER2-negative breast cancer from multiple centers were detected using RecurIndex assay, based on which the patients were assigned into low- and high-risk groups. The survival outcomes of low- and high-risk patients including those with and without adjuvant chemotherapy were compared, and the risk factors for recurrence and metastasis were identified. Results: Totally 445 patients were eligible for analysis. By contrast to high-risk patients, low-risk patients represented better 7-year recurrence-free survival (RFS), distant recurrence-free survival (DRFS) and local recurrence-free survival (LRFS) rates. For low-risk patients, no significant differences were shown between those with and without adjuvant chemotherapy in 7-year RFS, DRFS and LRFS rates. These differences were also inapparent between high-risk patients with and without adjuvant chemotherapy. The multivariate model revealed high-risk patients had a significantly elevated risk of recurrence and metastasis than those at low risk. Conclusion: HR-positive HER2-negative early breast cancer patients at low risk stratified by RecurIndex assay might be exempt from adjuvant chemotherapy. Whether adjuvant chemotherapy may derive survival benefits for high-risk patients still needs larger cohorts to verify.

18.
Breast ; 66: 8-14, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36084385

RESUMEN

PURPOSE: Triple-negative apocrine carcinoma (TNAC) is a sort of triple-negative breast cancer (TNBC) that is rare and prognosis of these patients is unclear. The present study constructed an effective nomogram to assist in predicting TNAC patients overall survival (OS). METHODS: A total of 373 TNAC patients from the surveillance, epidemiology, and end results (SEER) got extracted from 2010 to 2016 and were divided into training (n = 261) and external validation (n = 112) groups (split ratio, 7:3) randomly. A Cox regression model was utilized to creating a nomogram according to the risk factors affecting prognosis. The predictive capability of the nomogram was estimated with receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: Multivariate Cox regression analysis revealed age, surgery, chemotherapy, stage, and first malignant primary as independent predictors of OS. A prediction model was constructed and virtualized using the nomogram. The time-dependent area under the curve (AUC) showed satisfactory discrimination of the nomogram. Good consistency was shown on the calibration curves in OS between actual observations and the nomogram prediction. What's more, DCA showed that the nomogram had incredible clinical utility. Through separating the patients into groups of low and high risk group that connects with the risk system that shows a huge difference between the low-risk and high risk OS (P < 0.001). CONCLUSION: To predict the OS in TNAC patients, the nomogram utilizing the risk stratification system that is corresponding. These tools may help to evaluate patient prognosis and guide treatment decisions.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/terapia , Nomogramas , Células Epiteliales , Área Bajo la Curva , Movimiento Celular , Programa de VERF
19.
Cancer Manag Res ; 14: 2545-2559, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36060214

RESUMEN

Purpose: Solute carrier family 7, member 5 (SLC7A5) is reportedly a key gene in various tumors. However, the relationship between SLC7A5 and immune cell infiltration in breast cancer remains elusive. In this study, we investigated the expression levels and clinical value of SLC7A5 using the R package in breast cancer through the TCGA database. Methods: Public transcript data and clinical information of patients were downloaded from the TCGA database. Prognosis analysis was performed to explore the clinical value of SLC7A5 as well as drug sensitivity prediction and Gene Set Enrichment Analysis (GSEA). We also explored the correlations between SLC7A5 and immune infiltration as well as immune markers. Results: We observed that high SLC7A5 expression levels were related to poor survival. Our GSEA demonstrated that G protein-coupled receptor-ligand binding, interleukin signaling, neutrophil degranulation, amino acid and derivative metabolism, and Rho GTPase signaling were differentially enriched in the SLC7A5 high-expression phenotype. Patients in the low SLC7A5 expression group showed sensitivity to paclitaxel and doxorubicin. Conclusion: SLC7A5 could serve as a biomarker for breast cancer prognosis.

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