Organoids as a model system for researching human neuroendocrine tumor of the breast DOI Creative Commons
Dongyi Zhao, Xue Bai, Shida Zhu

и другие.

Cancer Cell International, Год журнала: 2024, Номер 24(1)

Опубликована: Дек. 27, 2024

Neuroendocrine tumors primarily consist of endocrine cells commonly located in neural tissue and the system. Primary neuroendocrine neoplasms breast are highly heterogeneous characterized by a diverse cell population. Their rarity poses considerable challenges studying their pathogenesis developing effective treatments. The surgical specimen was obtained from Chinese female patient diagnosed with tumor (NETB). We performed histological staining established NETB patient-derived organoids, which were subsequently used for staining, drug screen, Single-cell RNA sequencing. successfully organoids patient. Histological showed that morphological characteristics expression molecular biomarkers (ER, PR, HER2, Ki67, Syn, CgA) resembled those original tissue. exhibited varying sensitivities to seven different drugs. sequencing revealed significant heterogeneity functions among these organoids. This first instance establishing an organoid model NETB. Due high heterogeneity, this provides robust foundation clinical research. In future, it could serve as reliable tool disease pathology diagnosis, screening, genetic level studies.

Язык: Английский

Breast cancer: pathogenesis and treatments DOI Creative Commons
Xin Xiong,

Lewei Zheng,

Yu‐Qiang Ding

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 18, 2025

Abstract Breast cancer, characterized by unique epidemiological patterns and significant heterogeneity, remains one of the leading causes malignancy-related deaths in women. The increasingly nuanced molecular subtypes breast cancer have enhanced comprehension precision treatment this disease. mechanisms tumorigenesis progression been central to scientific research, with investigations spanning various perspectives such as tumor stemness, intra-tumoral microbiota, circadian rhythms. Technological advancements, particularly those integrated artificial intelligence, significantly improved accuracy detection diagnosis. emergence novel therapeutic concepts drugs represents a paradigm shift towards personalized medicine. Evidence suggests that optimal diagnosis models tailored individual patient risk expected are crucial, supporting era oncology for cancer. Despite rapid advancements increasing emphasis on clinical comprehensive update summary panoramic knowledge related disease needed. In review, we provide thorough overview global status including its epidemiology, factors, pathophysiology, subtyping. Additionally, elaborate latest research into contributing progression, emerging strategies, long-term management. This review offers valuable insights Cancer Research, thereby facilitating future progress both basic application.

Язык: Английский

Процитировано

14

Sequencing of high-frequency mutated genes in breast cancer (BRCA) and associated-functions analysis DOI
Xue‐Lian Li, Mei Yang, Liyuan Yang

и другие.

International Journal of Clinical and Experimental Pathology, Год журнала: 2025, Номер 18(2), С. 46 - 62

Опубликована: Янв. 1, 2025

Mutations or aberrant expression of genes in an organism tend not to be completely random and this cumulative effect predisposes the development malignant tumours. This study aims reveal possible high frequency mutated genes, then investigate their role development, prognosis, signalling pathway function drug resistance breast cancer. The cancer (BRCA) clinical samples were identified detected by high-throughput sequencing. High-frequency mutant counted. Gene profiles relationship with prognosis analysed throughout TCGA database. qRT-PCR was used analyse mRNA levels six high-frequency BRCA tissues cell lines. IHC protein tissues. linear interaction, single-cell layer clustering status influence immune infiltration degree among these bioinformatics analysis. STITCH cMAP datasets for gene interaction networks, association enrichment drug-transcriptome analyses. effects trastuzumab on proliferative capacity cells, as well determined CCK8 assay. that statistically found have mutations recruited present sequencing analysis included TP53, PIK3CA, NF1, TBX3, BRCA1 BRCA2. correlation further demonstrated using database: trend similar TCGA. showed BRCA2 higher tumor than normal samples, opposite a observed expressions displayed same IHC. Other results include 1) single resulted significant few overlapping regions; 2) different degrees infiltration; 3) between each other; 4) network had partially molecules; 5) PI3K key BRCA. Finally, proliferation ability confirmed optimal concentration its genes.

Язык: Английский

Процитировано

0

Neoadjuvant fuzuloparib combined with abiraterone for localized high-risk prostate cancer (FAST-PC): A single-arm phase 2 study DOI Creative Commons

Tingwei Zhang,

Beihe Wang, Wei Yu

и другие.

Cell Reports Medicine, Год журнала: 2025, Номер unknown, С. 102018 - 102018

Опубликована: Март 1, 2025

Highlights•Neoadjuvant PARPi + ARSi shows efficacy with manageable toxicity in high-risk PCa•Biallelic HRR/BRCA2 alterations correlate faster PSA decline•Post-treatment analysis reveals MYC suppression and reduced proliferation-related pathways•Drug-tolerant persister cells exhibit enhanced EMT AP-1 activationSummaryPreclinical studies suggest synergistic effects between androgen receptor inhibitors poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors. This phase 2 trial (NCT05223582) evaluates neoadjuvant fuzuloparib plus abiraterone 35 treatment-naive men localized prostate cancer. Patients receive six cycles of therapy followed by radical prostatectomy. Primary endpoints are pathological complete response (pCR) minimal residual disease (MRD, ≤5 mm). The combined pCR/MRD rate is 46% (95% confidence interval [CI]: 29%–63%), a 53% 2-year biochemical progression-free survival rate. Grade ≥3 adverse events occur 23% patients. Biallelic homologous recombination repair/BRCA2 prostate-specific antigen decline. Post-treatment genomic analyses reveal amplification proliferation markers, alongside activated epithelial-mesenchymal transition/activator protein 1 (AP-1) pathways. meets its primary endpoint, demonstrating feasibility preliminary efficacy, while exploratory biomarkers may guide future studies.Graphical abstract

Язык: Английский

Процитировано

0

MGAT4EP promotes tumor progression and serves as a prognostic marker for breast cancer DOI Creative Commons
Zhong Lin,

J.Z. Zhu,

Jie Chen

и другие.

Cancer Biology & Therapy, Год журнала: 2025, Номер 26(1)

Опубликована: Март 11, 2025

Breast cancer remains a global health challenge with varied prognoses despite treatment advancements. Therefore, this study explores the pseudogene MGAT4EP as potential biomarker and therapeutic target in breast cancer. Using TCGA data bioinformatics, was identified significantly overexpressed tissues associated poor prognosis. Multivariate Cox regression confirmed important prognostic factor. A clinical prediction model based on expression showed high accuracy for 1-, 3-, 5-year survival rates translated into nomogram application. Functional studies revealed that silencing via siRNA promoted apoptosis, inhibited migration invasion cells. RNA-seq, GSEA, GO analyses linked to apoptosis focal adhesion pathways. Notably, knock down of suppressed tumor growth metastasis xenograft lung models. Taken together, these findings establish an attractive metastatic provide promising treatment.

Язык: Английский

Процитировано

0

Precision Spatial Control of Tumor‐Stroma Interactions in Cancer Models via 3D Bioprinting for Advanced Research and Therapy DOI
Yan Li, Haijun Cui, Haitao Cui

и другие.

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Abstract As an emerging technology for modeling cancer tissue in vitro, 3D bioprinting facilitates precise spatial manipulation of cells and biomaterials, allowing the replication complex architectures accurate recapitulation tumor microenvironment (TME) features. This review initially elucidates mechanisms underlying tumorigenesis associated TME complexity, with a particular focus on roles stromal cell populations characteristics extracellular matrix (ECM) progression. Moreover, this work summarizes recent advances bioprinted models, emphasizing their application studying cell‐ECM interactions, stromal‐tumor crosstalk, vasculature formation investigating occurrence metastasis, as well utility high‐throughput drug screening therapeutic development. Finally, discusses advantages challenges creating biomimetic while providing insights into future development trajectories potential translational applications research personalized medicine. By focusing these critical dimensions, aims to highlight transformative role advancing vitro models ultimate goal improving treatment, prevention, patient outcomes.

Язык: Английский

Процитировано

0

Precision medicine for breast cancer: advances and challenges DOI
Xinyi Liu, Tian‐Jian Yu,

Zhi-Ming Shao

и другие.

Translational Breast Cancer Research, Год журнала: 2024, Номер 5, С. 35 - 35

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

1

Spatially defined microenvironment for engineering organoids DOI
Yilan Zhang,

Fukang Qi,

Peng Chen

и другие.

Biophysics Reviews, Год журнала: 2024, Номер 5(4)

Опубликована: Окт. 18, 2024

In the intricately defined spatial microenvironment, a single fertilized egg remarkably develops into conserved and well-organized multicellular organism. This observation leads us to hypothesize that stem cells or other seed cell types have potential construct fully structured functional tissues organs, provided cues are appropriately configured. Current organoid technology, however, largely depends on spontaneous growth self-organization, lacking systematic guided intervention. As result, structures replicated in vitro often emerge disordered sparse manner during phases. Although existing organoids made significant contributions many aspects, such as advancing our understanding of development pathogenesis, aiding personalized drug selection, well expediting development, their creating large-scale implantable tissue organ constructs, constructing multicomponent microphysiological systems, together with functioning at metabolic levels remains underutilized. Recent discoveries demonstrated definition factors not only induces directional migration but also formation assembloids multiple regional identities. opens new avenues for innovative engineering higher-order organoids. Concurrently, organization microenvironmental cues, physical stresses, mechanical loads, material composition, has been minimally explored. review delves burgeoning field focus control. It offers insight molecular principles, expected outcomes, applications, envisioning future perspective this domain.

Язык: Английский

Процитировано

0

Advancements in Organoid Culture Technologies: Current Trends and Innovations DOI
Y. Ji,

Yang Sun

Stem Cells and Development, Год журнала: 2024, Номер 33(23-24), С. 631 - 644

Опубликована: Ноя. 7, 2024

Organoids have emerged as valuable tools in investigating disease mechanisms, drug efficacy, and personalized medicine due to their capacity recapitulate crucial aspects of tissue physiology, including cell-cell interactions, heterogeneity, microenvironmental cues, responses. Despite broad applicability across various research domains, conventional organoid culture methods are plagued by several limitations that hinder progress. These include the inability faithfully recreate microenvironments, immune contexts, vascular systems. Fortunately, ongoing advancements techniques addressing these shortcomings. In this review, we provide a comprehensive overview current mainstream protocols. By evaluating protocols, researchers can identify most suitable experimental methods, thereby optimizing resource allocation outcomes.

Язык: Английский

Процитировано

0

Organoids as a model system for researching human neuroendocrine tumor of the breast DOI Creative Commons
Dongyi Zhao, Xue Bai, Shida Zhu

и другие.

Cancer Cell International, Год журнала: 2024, Номер 24(1)

Опубликована: Дек. 27, 2024

Neuroendocrine tumors primarily consist of endocrine cells commonly located in neural tissue and the system. Primary neuroendocrine neoplasms breast are highly heterogeneous characterized by a diverse cell population. Their rarity poses considerable challenges studying their pathogenesis developing effective treatments. The surgical specimen was obtained from Chinese female patient diagnosed with tumor (NETB). We performed histological staining established NETB patient-derived organoids, which were subsequently used for staining, drug screen, Single-cell RNA sequencing. successfully organoids patient. Histological showed that morphological characteristics expression molecular biomarkers (ER, PR, HER2, Ki67, Syn, CgA) resembled those original tissue. exhibited varying sensitivities to seven different drugs. sequencing revealed significant heterogeneity functions among these organoids. This first instance establishing an organoid model NETB. Due high heterogeneity, this provides robust foundation clinical research. In future, it could serve as reliable tool disease pathology diagnosis, screening, genetic level studies.

Язык: Английский

Процитировано

0