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1.
Elife ; 132024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995840

ABSTRACT

Aberrant alternative splicing is well-known to be closely associated with tumorigenesis of various cancers. However, the intricate mechanisms underlying breast cancer metastasis driven by deregulated splicing events remain largely unexplored. Here, we unveiled that RBM7 is decreased in lymph node and distant organ metastases of breast cancer as compared to primary lesions and low expression of RBM7 is correlated with the reduced disease-free survival of breast cancer patients. Breast cancer cells with RBM7 depletion exhibited an increased potential for lung metastasis compared to scramble control cells. The absence of RBM7 stimulated breast cancer cell migration, invasion, and angiogenesis. Mechanistically, RBM7 controlled the splicing switch of MFGE8, favoring the production of the predominant isoform of MFGE8, MFGE8-L. This resulted in the attenuation of STAT1 phosphorylation and alterations in cell adhesion molecules. MFGE8-L exerted an inhibitory effect on the migratory and invasive capability of breast cancer cells, while the truncated isoform MFGE8-S, which lack the second F5/8 type C domain had the opposite effect. In addition, RBM7 negatively regulates the NF-κB cascade and an NF-κB inhibitor could obstruct the increase in HUVEC tube formation caused by RBM7 silencing. Clinically, we noticed a positive correlation between RBM7 expression and MFGE8 exon7 inclusion in breast cancer tissues, providing new mechanistic insights for molecular-targeted therapy in combating breast cancer.


Subject(s)
Breast Neoplasms , NF-kappa B , RNA-Binding Proteins , Humans , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Female , NF-kappa B/metabolism , Cell Movement/genetics , Cell Line, Tumor , Alternative Splicing , Neoplasm Metastasis , Signal Transduction , Animals , Gene Expression Regulation, Neoplastic , Mice
2.
Anal Chim Acta ; 1317: 342916, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39030013

ABSTRACT

BACKGROUND: Protein misfolding and aggregation can lead to various diseases. Recent studies have shed light on the aggregated protein in breast cancer pathology, which suggests that it is crucial to design chemical sensors that visualize protein aggregates in breast cancer, especially in clinical patient-derived samples. However, most reported sensors are constrained in cultured cell lines. RESULTS: In this work, we present the development of two isophorone-based crystallization-induced-emission fluorophores for detecting proteome aggregation in breast cancer cell line and tissues biopsied from diseased patients, designated as A1 and A2. These probes exhibited viscosity sensitivity and recovered their fluorescence strongly at crystalline state. Moreover, A1 and A2 exhibit selective binding capacity and strong fluorescence for various aggregated proteins. Utilizing these probes, we detect protein aggregation in stressed breast cancer cells, xenograft mouse model of human breast cancer and clinical patient-derived samples. Notably, the fluorescence intensity of both probes light up in tumor tissues. SIGNIFICANCE: The synthesized isophorone-based crystallization-induced-emission fluorophores, A1 and A2, enable sensitive detection of protein aggregation in breast cancer cells and tissues. In the future, aggregated proteins are expected to become indicators for early diagnosis and clinical disease monitoring of breast cancer.


Subject(s)
Breast Neoplasms , Crystallization , Fluorescent Dyes , Proteome , Humans , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Animals , Female , Fluorescent Dyes/chemistry , Proteome/analysis , Proteome/chemistry , Mice , Protein Aggregates , Cell Line, Tumor , Mice, Nude
3.
Clin Breast Cancer ; 24(5): 392-398.e3, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38580572

ABSTRACT

Poly-ADP ribose polymerase inhibitor (PARPi) is approved for HER2-negative advanced breast cancer with BRCA1/2 mutation. In recent years, many studies have explored the application of PARPi in neoadjuvant therapy, but failed to reach a unified conclusion. PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase, and key oncological meetings for trials were searched for studies reporting neoadjuvant regimens with PARPi in HER2-negative breast cancer. Pathological complete response (pCR), residual cancer burden (RCB), breast-conservation surgery rate (BCSR), clinical response, and adverse events were extracted and pooled in a meta-analysis using the Mantel Haenszel random/fixed effects model. Subgroup analyses of pCR were conducted according to BRCA1/2 status, and hormone receptor (HR) status. Five studies (N = 1223) were included, the addition of PARPi to neoadjuvant regimens significantly increased pCR rates (HR 1.45, 95%CI 1.09-1.92, P = .01, I2 = 86%). In subgroup analysis, the addition of PARPi increased the pCR rate both in HR-positive (n = 383) and HR-negative (n = 431) subgroups, which showed a dominant effect of PARPi regardless of HR status (HR 2.07, 95%CI 1.33-3.23, P = .001, I2 = 0%; HR 1.85, 95%CI 1.39-2.26, P < .0001, I2 = 0%, respectively). However, when we performed a subgroup analysis based on the status of BRCA1/2, no further benefit for PARPi was found. Adverse reactions were generally tolerable. Other outcome indexes, including RCB, clinical response, BCSR, and PARPi did not show a clinical benefit. Regardless of BRCA1/2 status, PARPi in neoadjuvant therapy, can improve the pCR rate of HER2-negative breast cancer, especially in HR-positive patients. Thus, we should have performed larger randomized trials and provided a stronger evidence-based basis.


Subject(s)
Breast Neoplasms , Neoadjuvant Therapy , Poly(ADP-ribose) Polymerase Inhibitors , Receptor, ErbB-2 , Female , Humans , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Neoadjuvant Therapy/methods , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Receptor, ErbB-2/metabolism , Treatment Outcome
4.
J Colloid Interface Sci ; 664: 938-945, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38503079

ABSTRACT

Supramolecular self-assembly is ubiquitous in living system and is usually controlled to proceed in time and space through sophisticated reaction-diffusion processes, underpinning various vital cellular functions. In this contribution, we demonstrate how spatiotemporal self-assembly of supramolecular hydrogels can be realized through a simple reaction-diffusion-mediated transient transduction of pH signal. In the reaction-diffusion system, a relatively faster diffusion of acid followed by delayed enzymatic production and diffusion of base from the opposite site enables a transient transduction of pH signal in the substrate. By coupling such reaction-diffusion system with pH-sensitive gelators, dynamic supramolecular hydrogels with tunable lifetimes are formed at defined locations. The hydrogel fibers show interesting dynamic growing behaviors under the regulation of transient pH signal, reminiscent of their biological counterpart. We further demonstrate a proof-of-concept application of the developed methodology for dynamic information encoding in a soft substrate. We envision that this work may provide a potent approach to enable transient transduction of various chemical signals for the construction of new colloidal materials with the capability to evolve their structures and functionalities in time and space.

5.
Cancer Gene Ther ; 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38409585

ABSTRACT

Dysregulated cellular proliferation represents a hallmark feature across all cancers. Aberrant activation of the cyclin-dependent kinase 4 and 6 (CDK4/6) pathway, independent of mitogenic signaling, engenders uncontrolled breast cancer cell proliferation. Consequently, the advent of CDK4/6 inhibition has constituted a pivotal milestone in the realm of targeted breast cancer therapy. The combination of CDK4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) has emerged as the foremost therapeutic modality for patients afflicted with hormone receptor-positive (HR + )/HER2-negative (HER2-) advanced breast cancer. At present, the Food and Drug Administration (FDA) has sanctioned various CDK4/6i for employment as the primary treatment regimen in HR + /HER2- breast cancer. This therapeutic approach has demonstrated a substantial extension of progression-free survival (PFS), often amounting to several months, when administered alongside endocrine therapy. Within this comprehensive review, we systematically evaluate the utilization strategies of CDK4/6i across various subpopulations of breast cancer and explore potential therapeutic avenues following disease progression during application of CDK4/6i therapy.

6.
Sheng Wu Gong Cheng Xue Bao ; 40(2): 446-457, 2024 Feb 25.
Article in Chinese | MEDLINE | ID: mdl-38369832

ABSTRACT

In recent years, microneedles have emerged as a drug delivery technology that holds great research value and application potential due to their minimally invasive, painless, user-friendly, and efficient characteristics. The technology of microneedles has rapidly evolved over the past 20 years, allowing customization of shape, composition, mechanical properties, and unique functions to meet diverse needs. With the ability to minimally invasively traverse various biological barriers, researchers have explored the applications of microneedles in various tissues and organs beyond the skin. This article summarizes the research progress on the use of microneedles for drug delivery in tissues such as eyes, blood vessel, and heart. By presenting these cutting-edge research to readers, we hope to promote the development and application of microneedle technology.


Subject(s)
Needles , Skin , Administration, Cutaneous , Microinjections , Drug Delivery Systems
7.
Micromachines (Basel) ; 14(10)2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37893293

ABSTRACT

This paper explores advanced shape control techniques for ultra-lightweight electro-actuated polymers with composite ferroelectric thin films. It begins with an overview of PVDF-TrFE film actuators used in the development of thin-shell composites, emphasizing the need to overcome constraints related to the electrode size for successful scalability. Strain generation in thin-film actuators is investigated, including conventional electrode-based methods and non-contact electron flux excitation. Numerical studies incorporate experimentally calibrated ferroelectric parameters, modeling non-contact actuation with an equivalent circuit representation. The potential distribution generated by electron flux injection highlights its potential for reducing print-through actuation issues. Additionally, the paper outlines a vision for the future of large thin-shell reflectors by integrating the discussed methods for charging ferroelectric polymer films. A hierarchical control strategy is proposed, combining macro- and micro-scale techniques to rectify shape errors in lightweight reflectors. These strategies offer the potential to enhance precision and performance in future spaceborne observation systems, benefiting space exploration and communication technologies.

8.
Micromachines (Basel) ; 14(9)2023 Sep 09.
Article in English | MEDLINE | ID: mdl-37763919

ABSTRACT

This paper focuses on the change of morphing capabilities for a unimorph deformable mirror impacted by environmental factors, which works in space for active optics applications. Various aspects of disturbing sources are considered, including complex thermal and mechanical conditions on ferroelectric behaviours of strain actuation, and influences of preconfigured initial shapes and stress-induced geometric stiffness on the structural rigidity of the mirror; changes on both the perturbed shape and the Jacobian matrix are discussed. Those variations are regarded as uncertainties in the design of control methods with both open-loop and iterative control strategies tested in the quasi-static range.

9.
Sensors (Basel) ; 23(2)2023 Jan 12.
Article in English | MEDLINE | ID: mdl-36679686

ABSTRACT

Shipborne atomic gravimeter (SAG) is an instrument that can directly measure absolute gravity in dynamic environments. As a new type of gravity sensor, a standard method for evaluating its detailed performance has not been proposed and the detailed performance of SAG was rarely reported. In this paper, a system of dynamic gravity measurement, which was integrated with a home-made atomic gravimeter, is demonstrated, and a novel and simple method for testing the performance of SAG on the lake based on the modulated Coriolis effect is put forward. Firstly, in the state of ship mooring, a tilt modulation of the gravity sensor has been realized to make sure the Raman wave vector is parallel to the gravity axis. Moreover, a comparison between the measurement result of CG-5 and SAG has also been carried out to evaluate the accuracy of the SAG. Then, the Coriolis effect modulating experiment is carried out with various routes on lake to test its performance in dynamic environments. In the ship mooring state, the accuracy has been demonstrated to be 0.643 mGal. The internal consistency reliabilities are evaluated to be 0.8 mGal and 1.2 mGal under the conditions of straight line and circle navigation, respectively.


Subject(s)
Coriolis Force , Gravitation , Ships
10.
Sci Total Environ ; 860: 160478, 2023 Feb 20.
Article in English | MEDLINE | ID: mdl-36574551

ABSTRACT

The contradiction between population growth and soil degradation has been increasingly prominent, such that novel fertilizers (e.g., biochar and microbial fertilizers) should be urgently developed. Biochar is a promising fertilizer carrier for microbial fertilizers due to its porous structure. However, the preparation and mechanisms of the effects of biochar-based microbial fertilizers have been rarely investigated. In this study, biochar, Bacillus, and exogenous N-P-K fertilizers served as the raw materials to prepare biochar-based microbial fertilizers (BCMFs) by optimizing the preparation methods and the process parameters. Moreover, the release patterns of N-P-K were analyzed. A pot experiment was performed on pakchoi to examine the effect of the BCMFs and explore its synergistic effect on soil fertility. The results of this study indicated that adsorption by biochar maintained bacterial activity, whereas the granulation process reduced bacterial activity. The adsorption-granulation process increased the content of total nitrogen and organic matter in the soil while enhancing the slow-release effect of the BCMFs. The Elovich model was capable of describing the nitrogen release of the BCMFs, including the diffusion and chemical processes. As indicated by the result of the column leaching experiment, the BCMFs stopped nutrient leaching more significantly than the conventional fertilizers (CF), especially in stopping N and P leaching. The use of the BCMFs improved the available soil nutrients and soil quality while enhancing the abundance of bacteria correlated with carbon and nitrogen metabolism in the soil. Moreover, a 20 % reduction in the use of the BCMFs did not significantly affect the soil available N and P and the growth status of pakchoi. The result of redundancy analysis indicated that the cation exchange capacity (CEC), NH4+-N, NO3--N, ß-glucosidase (BG), urease (URE), and alkaline phosphatase (AlkP) were the six critical environmental factors for the microbial community structure and could explain 94.8 % of the variance. The BCMFs up-regulated the levels of the above six factors, especially CEC and BG, thus improving the soil quality and enhancing the soil fertility.


Subject(s)
Fertilizers , Soil , Soil/chemistry , Fertilizers/analysis , Charcoal/chemistry , Nitrogen/analysis , Bacteria , Nutrients/analysis , Soil Microbiology
11.
Materials (Basel) ; 17(1)2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38203989

ABSTRACT

Electrically driven multi-stable cholesteric liquid crystals can be used to adjust the transmittance of incident light. Compared with the traditional liquid crystal optical devices, the multi-stable devices only apply an electric field during switching and do not require a continuous electric field to maintain the various optical states of the device. Therefore, the multi-stable devices have low energy consumption and have become a research focus for researchers. However, the multi-stable devices still have shortcomings before practical application, such as contrast, switching time, and mechanical strength. In this article, the latest research progress on electrically driven multi-stable cholesteric liquid crystals is reviewed, including electrically driven multi-stable modes, performance optimization, and applications. Finally, the challenges and opportunities of electrically driven multi-stable cholesteric liquid crystals are discussed in anticipation of contributing to the development of multi-stable liquid crystal devices.

12.
Molecules ; 27(20)2022 Oct 16.
Article in English | MEDLINE | ID: mdl-36296533

ABSTRACT

Blue-phase liquid crystal (BPLC) is considered as the next-generation liquid crystal display material, but its practical application is seriously affected by a narrow temperature range and a long research period. In this paper, we used inkjet printing technology to prepare BPLC materials with high throughput, and try to use machine vision technology to test BPLC with high throughput. The "standard curve method" for establishing each printing channel and the "vector matching method" for searching the chromaticity value of the minimum distance were proposed to improve the accuracy of inkjet printing BPLC materials. For a large number of sample-phase images, we propose a machine learning method to identify the liquid crystal phase. In this paper, for the first time, the high-throughput preparation and high-throughput detection of 1080 BPLC samples with five common components by a comprehensive experimental method has been successfully realized. The results are helpful to improve the research efficiency of blue-phase materials and provide a theoretical basis and practical guidance for rapid screening of multi-component BPLC materials.

13.
Psychol Aging ; 37(7): 843-847, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36174175

ABSTRACT

The opportunity to exert control in one's environment is desirable, and individuals are willing to seek out control, even at a financial cost. Additionally, control-related activation of reward regions in the brain and the positive affect associated with the opportunity to exert control suggest that control is rewarding. The present study explores whether there are age-related differences in the preference for control. Older and younger adults chose whether to maintain control and play a guessing game themselves or to cede this control to the computer. Maintaining and ceding control were associated with different amounts of monetary reward that could be banked upon a successful guess. This required participants to weigh the value associated with control compared to monetary rewards. We found that older adults preferred control and traded monetary reward for control, similar to younger adults. The results suggest that the preference for exerting control may be preserved across age. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Aging , Reward , Humans , Aged , Aging/physiology , Brain/physiology
14.
Breast ; 66: 31-39, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36096071

ABSTRACT

INTRODUCTION: Platinum-based chemotherapy (PBC) remains the mainstay of treatments for triple-negative breast cancer (TNBC). TNBC is a heterogeneous group, the issue of whether BRCA1/2 mutation carriers have a particular sensitivity to platinum agents is inconclusive. We conducted a meta-analysis to explore the relationship between BRCA1/2 mutation and PBC susceptibility in individuals with TNBC, aiming to gain more information on the size of the benefit of PBC in BRCA1/2 mutation carriers. MATERIALS AND METHODS: All studies applying PBC with a subgroup of BRCA1/2 status were included. All endpoints, including pCR and RCB in the neoadjuvant phase, DFS in the adjuvant phase, ORR, PFS, and OS in the advanced phase, were assessed using HRs and 95% Cl. RESULTS: From the 22 studies included, there were 2158 patients with TNBC, with 392 (18%) bearing the BRCA1/2 gene mutation. Based on 13 studies applying neoadjuvant PBC, we discovered that BRCA1/2 mutation was substantially associated with a 17.6% increased pCR rate (HR 1.32, 95% CI 1.17-1.49, p < 0.00001; I2 = 51%). Same result was observed in RCB0/I index (HR 1.38, 95% CI 1.08-1.76, P = 0.009; I2 = 0%). The meta-analysis of 6 trials addressing advanced therapy revealed that ORR rates were significantly higher in patients with BRCA1/2 mutation (HR 1.91, 95% CI 1.48-2.47, p < 0.00001; I2 = 32%), as well as PFS(HR 1.13, 95% CI 0.81-1.57, P = 0.47; I2 = 0%) and OS (HR 1.89, 95% CI 1.22-2.92, P = 0.004; I2 = 0%). CONCLUSION: According to our meta-analysis of 22 trials in TNBC, BRCA1/2 mutation carriers were significantly more sensitive to PBC regimens, especially in neoadjuvant and advanced therapy.


Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Humans , Female , Platinum/therapeutic use , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics , Breast Neoplasms/drug therapy , Mutation , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoadjuvant Therapy , BRCA1 Protein/genetics
15.
Front Oncol ; 12: 882784, 2022.
Article in English | MEDLINE | ID: mdl-36033499

ABSTRACT

Objective: Triple-negative breast cancer (TNBC) is distinguished by early recurrence and metastases, a high proclivity for treatment resistance, and a lack of targeted medicines, highlighting the importance of developing innovative therapeutic techniques. Salvia chinensis Benth (SCH) has been widely studied for its anticancer properties in a variety of cancers. However, its significance in TNBC treatment is rarely discussed. Our study investigated the anticancer effect of SCH on TNBC and the underlying mechanisms. Methods: First, we used clonogenic, cell viability, flow cytometry, and Transwell assays to assess the effect of SCH on TNBC. Bioinformatic studies, especially network pharmacology-based analysis and RNA sequencing analysis, were performed to investigate the constituents of SCH and its molecular mechanisms in the suppression of TNBC. High-performance liquid chromatography and thin-layer chromatography were used to identify two major components, quercetin and ß-sitosterol. Then, we discovered the synergistic cytotoxicity of quercetin and ß-sitosterol and assessed their synergistic prevention of cell migration and invasion. Breast cancer xenografts were also created using MDA-MB-231 cells to test the synergistic therapeutic impact of quercetin and ß-sitosterol on TNBC in vivo. The impact on the DNA damage and repair pathways was investigated using the comet assay and Western blot analysis. Results: Our findings showed that SCH decreased TNBC cell growth, migration, and invasion while also inducing cell death. We identified quercetin and ß-sitosterol as the core active components of SCH based on a network pharmacology study. According to RNA sequencing research, the p53 signaling pathway is also regarded as a critical biological mechanism of SCH treatment. The comet assay consistently showed that SCH significantly increased DNA damage in TNBC cells. Our in vivo and in vitro data revealed that the combination of quercetin and ß-sitosterol induced synergistic cytotoxicity and DNA damage in TNBC cells. In particular, SCH particularly blocked the inter-strand cross-link repair mechanism and the double-strand breach repair caused by the homologous recombination pathway, in addition to inducing DNA damage. Treatment with quercetin and ß-sitosterol produced similar outcomes. Conclusion: The current study provides novel insight into the previously unknown therapeutic potential of SCH as a DNA-damaging agent in TNBC.

16.
Sensors (Basel) ; 22(16)2022 Aug 18.
Article in English | MEDLINE | ID: mdl-36015933

ABSTRACT

The cold atom gravimeter (CAG) has proven to be a powerful quantum sensor for the high-precision measurement of gravity field, which can work stably for a long time in the laboratory. However, most CAGs cannot operate in the field due to their complex structure, large volume and poor environmental adaptability. In this paper, a home-made, miniaturized CAG is developed and a truck-borne system based on it is integrated to measure the absolute gravity in the field. The measurement performance of this system is evaluated by applying it to measurements of the gravity field around the Xianlin reservoir in Hangzhou City of China. The internal and external coincidence accuracies of this measurement system were demonstrated to be 35.4 µGal and 76.7 µGal, respectively. Furthermore, the theoretical values of the measured eight points are calculated by using a forward modeling of a local high-resolution digital elevation model, and the calculated values are found to be in good agreement with the measured values. The results of this paper show that this home-made, truck-borne CAG system is reliable, and it is expected to improve the efficiency of gravity surveying in the field.

17.
Front Surg ; 9: 837848, 2022.
Article in English | MEDLINE | ID: mdl-35656090

ABSTRACT

Background: Breast cancer (BC) is the most common cancer among women worldwide, with enormous heterogeneity. Pyroptosis has a significant impact on the development and progression of tumors. Nonetheless, the possible correlation between pyroptosis-related genes (PRGs) and the BC immune microenvironment has yet to be investigated. Materials and methods: In The Cancer Genome Atlas Breast Cancer cohort, 38 PRGs were shown to be significantly different between malignant and non-malignant breast tissues. The 38 PRGs' consensus clustering grouped 1,089 individuals into two pyroptosis-related (PR) patterns. Using univariate and LASSO-Cox analyses, a PR five-gene predictive signature was constructed based on the differentially expressed genes between two clusters. The tools estimation of stromal and immune cells in malignant tumours using expression data (ESTIMATE), cell type identification by estimating relative subsets Of RNA transcripts (CIBERSORT), and single-sample gene set enrichment analysis (ssGSEA) were used to investigate the BC tumor microenvironment (TME). Results: In TME, the two PR clusters displayed distinct clinicopathological characteristics, survival outcomes, and immunocyte infiltration features. The developed five-signature model (SEMA3B, IGKC, KLRB1, BIRC3, and PSME2) classified BC patients into two risk groups based on the estimated median risk score. Patients in the low-scoring category had a higher chance of survival and more extensive immunocyte infiltration. An external validation set can yield similar results. Conclusion: Our data suggest that PRGs have a significant impact on the BC immunological microenvironment. The PR clusters and associated predictive signature stimulate additional research into pyroptosis in order to optimize therapeutic strategies for BC patients and their responses to immune therapy.

18.
Mol Biol Rep ; 49(7): 6155-6160, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35384625

ABSTRACT

BACKGROUND: Resistance to HER2-targeted therapy is a critical issue in breast cancer that must be addressed immediately. PIK3R1 mutations are more common in Chinese breast cancer patients (17%, 25/147, Fudan University Shanghai Cancer Center FUSCC vs. 1.8%, 87/4602, TCGA all breast cancer studies). However, very limited information is available on the relationship between PIK3R1 mutation status and resistance to HER2-targeted therapies in patients with HER2-positive breast cancer. CASE REPORT: We present a case of a HER2-positive advanced breast cancer patient with the PIK3R1EY451delinsD mutation who developed resistance to HER2-targeted therapy and had a better response to everolimus combined with trastuzumab and carboplatin. CONCLUSIONS: To the best of our knowledge, this is the first study to show that the PIK3R1EY451delinsD mutation confers resistance to anti-HER2 therapy in breast cancer and that combining with everolimus treatment may overcome this resistance mechanism. We hypothesize that the PIK3R1EY451delinsD mutation is associated with the resistance to anti-HER2 therapy, and that this mutation merits further investigation as a clinical biomarker and therapeutic target.


Subject(s)
Breast Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , China , Class Ia Phosphatidylinositol 3-Kinase/therapeutic use , Drug Resistance, Neoplasm/genetics , Everolimus/therapeutic use , Female , Humans , Receptor, ErbB-2/genetics , Trastuzumab/therapeutic use
19.
Front Oncol ; 12: 1099164, 2022.
Article in English | MEDLINE | ID: mdl-36686812

ABSTRACT

Approximately 75% of patients with advanced breast cancer develop bone metastasis, which significantly affects both the quality of life and the survival rate of patients. Accurate determination of the status of bone metastases is important for developing treatment strategies and the prognosis of the disease. Here, we report the case of a 33-year-old patient with advanced metastatic breast cancer (MBC) and multiple bone metastases, in which advanced first-line endocrine therapy and second-line chemotherapy were both considered unsuccessful according to the efficacy evaluation by conventional imaging. Considering the possibility of bone pseudoprogression, the original endocrine scheme was reapplied, and bone metastases achieved a great response of non-complete response (CR)/non-progressive disease (PD). This case showed that, in the course of therapy for the disease, if bone scintigraphy (BS) shows increased lesion density or new lesions, this probably indicates a favorable response (osteoblastic repair of osteolytic lesions) to therapy, and not the worsening of metastatic lesions, called bone pseudoprogression. This paper will provide new insights into strategies for the treatment of bone metastasis and shows the significance of distinguishing osteoblastic bone repair from real bone lesion progression in clinical settings.

20.
Math Biosci Eng ; 18(6): 8331-8353, 2021 09 23.
Article in English | MEDLINE | ID: mdl-34814302

ABSTRACT

BACKGROUND: Metastasis-Associated in Colon Cancer 1(MACC1) is a validated biomarker for metastasis and is linked to survival. Although extensive experimental evidence indicates an association between MACC1 and diverse cancers, no pan-cancer analyses have yet been performed for this marker, and the role of MACC1 in immunology remains unknown. MATERIAL AND METHODS: In our study, we performed the analysis of MACC1 expression and its influence on prognosis using multiple databases, including TIMER2, GEPIA2, Kaplan-Meier plotter. MACC1 promoter methylation levels were evaluated using the UALCAN database. Based on the TCGA database, we explored the relationship between MACC1 and tumor mutational burden (TMB), microsatellite instability (MSI), immune checkpoints using the R programming language. We evaluated the association between MACC1 and immune infiltration via TIMER and UALCAN. RESULTS: Our results revealed that abnormal DNA methylation may be an important cause for the different expression of MACC1 across cancer types. Meanwhile, we explored the potential oncogenic roles of MACC1 and found significant prognostic value. MACC1 may be related to T-cell function and the polarization of tumor-associated macrophages, especially in STAD and LGG. Its expression was associated with immune infiltration and was found to be closely related to immune checkpoint-associated genes, especially CD274 and SIGLEC15, indicating that MACC1 may be a potential immune therapeutic target for several malignancies. Our paper reveals for the first time the relationship between MACC1 and cancer immunology. CONCLUSIONS: MACC1 might act as a predictor for the immune response in cancer patients, and could also represent a new potential immunotherapeutic target.


Subject(s)
Colonic Neoplasms , Trans-Activators , Biomarkers, Tumor , Colonic Neoplasms/genetics , Humans , Prognosis , Transcription Factors/genetics
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