Pathology, research and practice最新文献_第6页

Deciphering the significance of tumor necrosis and developing a grading system in combined hepatocellular-cholangiocarcinoma: A multicenter pathological study 解读肝细胞胆管合并癌肿瘤坏死的意义并建立分级系统：一项多中心病理研究。

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2026-02-01 Epub Date: 2025-12-16 DOI: 10.1016/j.prp.2025.156335

Han Wang , You-Wen Qian , Xia Sheng , Chun-Yan Xia , Hong-Zhen Chen , Zhen-Yu Cao , Hua Yu , Ying-Ying Zhou , Wen-Ming Cong , Miao-Xia He , Hui Dong

Background

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) lacks standardized pathological diagnostic paradigm. The significance of tumor necrosis in cHCC-CCA remains undefined. This study aimed to decipher its role and develop a practical grading system.

Methods

A multicenter analysis was conducted on 307 cHCC-CCA patients. Tumor necrosis was pathologically graded as: TN1 (no necrosis, N = 35), TN2 (focal necrosis; maximum diameter of a single focus ≤0.55 cm/one low-power field, N = 129), and TN3 (extensive necrosis; >0.55 cm, N = 143). Associations between tumor necrosis and clinicopathological features, recurrence-free survival (RFS), overall survival (OS), early RFS (≤2 years), and late RFS (>2 years) were assessed. The impact of postoperative adjuvant transarterial chemoembolization (PA-TACE) was also evaluated.

Results

Higher necrosis grades (TN2/TN3) were significantly associated with aggressive tumor characteristics, including larger tumor size, vascular invasion, and lymph node metastasis. TN3 patients had the worst median RFS (0.28 years) and OS (1.36 years), compared to TN2 (RFS: 0.68 years; OS: 2.64 years) and TN1 (RFS: 1.46 years; OS: not reached). The grading system was an independent prognostic factor for RFS, OS, and early RFS in multivariate analysis. PA-TACE significantly improved early RFS in the TN2/TN3 groups and RFS in the TN3 group specifically, but not in the TN1 group.

Conclusions

Tumor necrosis in cHCC-CCA indicates aggressive tumor biology and poorer outcomes. The proposed three-tier grading system provides robust prognostic stratification. PA-TACE benefits patients with significant necrosis (TN2/TN3), particularly in preventing early recurrence. Standardized assessment of tumor necrosis is recommended to optimize risk stratification and guide adjuvant therapy decisions for cHCC-CCA patients.

背景：肝细胞-胆管合并癌（cHCC-CCA）缺乏标准化的病理诊断模式。肿瘤坏死在cHCC-CCA中的意义尚不明确。本研究旨在解读其作用，并建立一套实用的分级体系。方法：对307例cHCC-CCA患者进行多中心分析。肿瘤坏死病理分级为：TN1（无坏死，N = 35）、TN2（局灶性坏死，单灶最大直径≤0.55 cm/一个低倍视场，N = 129）、TN3（广泛坏死，>0.55 cm, N = 143）。评估肿瘤坏死与临床病理特征、无复发生存期（RFS）、总生存期（OS）、早期RFS（≤2年）和晚期RFS （bb0 ~ 2年）之间的关系。术后辅助经动脉化疗栓塞（PA-TACE）的影响也进行了评估。结果：较高的坏死分级（TN2/TN3）与肿瘤的侵袭性特征显著相关，包括肿瘤大小较大、血管侵犯和淋巴结转移。与TN2 （RFS: 0.68年；OS: 2.64年）和TN1 （RFS: 1.46年；OS：未达到）相比，TN3患者的中位RFS（0.28年）和OS（1.36年）最差。在多变量分析中，分级系统是RFS、OS和早期RFS的独立预后因素。PA-TACE显著改善TN2/TN3组的早期RFS，特别是TN3组的RFS，但TN1组没有。结论：cHCC-CCA肿瘤坏死提示肿瘤生物学侵袭性，预后较差。建议的三层分级系统提供了可靠的预后分层。PA-TACE对显著坏死（TN2/TN3）患者有益，特别是在预防早期复发方面。建议对肿瘤坏死进行标准化评估，以优化风险分层，指导cHCC-CCA患者的辅助治疗决策。

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引用次数: 0

Extracellular vesicles in tumor microenvironment modulation and clinical diagnosis 细胞外囊泡对肿瘤微环境的调节及临床诊断。

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2026-02-01 Epub Date: 2025-12-24 DOI: 10.1016/j.prp.2025.156339

Huan Liu , Dong Niu , Tong-Yao Yu , Yu-Hua Wang , Kun-Lin Ran , Yan-Hua Liu , Da-Chuan Yin , Chen-Yan Zhang

Extracellular vesicles (EVs) are key drivers of tumor metastasis and colonization. Their cargo, consisting of proteins, nucleic acids, and other biomolecules, functions as molecular messengers that trigger the epithelial-mesenchymal transition (EMT) process in tumor cells and facilitate immune evasion by releasing immunosuppressive factors to promote immune escape. Additionally, EVs influence intercellular interactions within the tumor microenvironment, facilitating angiogenesis, increasing vascular permeability, and supplying nutrients and oxygen to support tumor growth and metastasis. During metastasis, EVs protect circulating tumor cells (CTCs) from shear forces in the vascular network and attacks from the immune system. Furthermore, tumor-derived EVs facilitate the establishment of pre-metastatic niches (PMNs), thereby facilitating organ-specific metastasis. In this review, we overview the biogenesis and functions of EVs, as well as various factors that regulate their secretion. We systematically review tumor-derived EV functions in tumor progression, and also the effects of their interactions with other cells (such as adipocytes, immune cells, fibroblasts, and mesenchymal stem cells) in the tumor microenvironment was clarified. Additionally, we evaluate the diagnostic and prognostic potential of EVs as biomarkers for early tumor detection. The review also summarizes validated EV-associated biomarkers, offering a valuable foundation for the development of EV-based strategies in cancer diagnosis and therapy.

细胞外囊泡（EVs）是肿瘤转移和定植的关键驱动因素。它们的货物由蛋白质、核酸和其他生物分子组成，作为分子信使，在肿瘤细胞中触发上皮-间质转化（EMT）过程，并通过释放免疫抑制因子促进免疫逃逸，促进免疫逃逸。此外，ev影响肿瘤微环境中的细胞间相互作用，促进血管生成，增加血管通透性，并提供营养和氧气以支持肿瘤生长和转移。在转移过程中，ev保护循环肿瘤细胞（ctc）免受血管网络中的剪切力和免疫系统的攻击。此外，肿瘤来源的ev促进了转移前生态位（pmn）的建立，从而促进了器官特异性转移。本文就ev的生物发生、功能以及调控其分泌的各种因素作一综述。我们系统地回顾了肿瘤源性EV在肿瘤进展中的功能，并阐明了它们在肿瘤微环境中与其他细胞（如脂肪细胞、免疫细胞、成纤维细胞和间充质干细胞）相互作用的影响。此外，我们评估了ev作为早期肿瘤检测的生物标志物的诊断和预后潜力。本文还总结了验证的ev相关生物标志物，为开发基于ev的癌症诊断和治疗策略提供了有价值的基础。

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引用次数: 0

Tumoroid-derived extracellular vesicles for prognosis and therapeutics: A valuable tool in precision medicine 肿瘤来源的细胞外囊泡的预后和治疗：一个有价值的工具，在精密医学

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2026-02-01 Epub Date: 2025-12-11 DOI: 10.1016/j.prp.2025.156332

Vijay Murali Ravi Mythili , ArulJothi Kandasamy Nagarajan , Vasanth Kanth Loganathbabu Thasma , Shriya Pattabiram , Kumaran Kasinathan , Ramya Lakshmi Rajendran , Anand Krishnan , Prakash Gangadaran , Byeong-Cheol Ahn

Precision medicine has transformed healthcare by tailoring treatment plans to an individual’s genetic profile, in contrast to standardized therapies. Patient-derived tumoroids facilitate cancer research, while extracellular vesicles (EVs) provide insights into disease states. EVs from tumoroids serve as diagnostic tools for cancer, reflecting gene mutations and enabling minimally invasive tracking of disease progression. Artificial Intelligence (AI) enhances precision medicine by analyzing extensive datasets derived from tumors and EVs, thereby advancing cancer detection and therapy. The tumor microenvironment (TME) plays a pivotal role in tumor development and is studied using patient-derived organoids (PDOs), which accurately recapitulate tissue function and support drug screening and personalized treatment strategies. Integrating precision medicine with AI-driven analysis of tumoroids and EVs holds the potential to improve patient outcomes and quality of life through personalized treatment approaches.

与标准化治疗相比，精准医疗通过根据个人基因特征定制治疗计划，改变了医疗保健。患者来源的类肿瘤促进了癌症研究，而细胞外囊泡（EVs）提供了对疾病状态的洞察。来自类肿瘤的ev可作为癌症的诊断工具，反映基因突变并实现对疾病进展的微创跟踪。人工智能（AI）通过分析来自肿瘤和ev的大量数据集来增强精准医疗，从而推进癌症的检测和治疗。肿瘤微环境（tumor microenvironment， TME）在肿瘤发展中起着至关重要的作用，人们利用患者源性类器官（patient-derived organoid, PDOs）来研究肿瘤微环境，这些器官能准确地概括组织功能，支持药物筛选和个性化治疗策略。将精准医疗与人工智能驱动的类肿瘤和ev分析相结合，有可能通过个性化治疗方法改善患者的预后和生活质量。

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引用次数: 0

The advancements in targeted therapeutic strategies for breast cancer via intervention of natural molecules: An insight into cellular and molecular mechanisms 通过自然分子干预的乳腺癌靶向治疗策略的进展：对细胞和分子机制的洞察。

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2026-02-01 Epub Date: 2025-12-23 DOI: 10.1016/j.prp.2025.156338

Mohammed Kaleem , Purushottam Gangane , Md Ali Mujtaba , Aachal Kanekar , Naiyer Shahzad , Abdullah R. Alzahrani , Ameeduzzafar Zafar , Aftab Ahmad

Breast cancer (BC) is the most common cancer and a major cause of cancer-related deaths in women worldwide. Its significant molecular heterogeneity leads to different response rates, leaving standard therapy approaches comparatively ineffective. Recent evidence highlights the promise of natural compound–based therapies in modulating oncogenic signaling, regulating epigenetic mechanisms, and reshaping the tumor microenvironment. This review systematically explores the anticancer potential of bioactive phytochemicals, including curcumin, resveratrol, thymoquinone, and berberine, in BC. These agents exhibit pleiotropic mechanisms such as promoting apoptosis (e.g., via p53 activation), suppressing angiogenesis (e.g., through VEGF downregulation), and reversing chemoresistance (e.g., by inhibiting the PI3K/AKT/mTOR axis). The role of epigenetic regulation is explored, focusing on DNA methylation, histone modifications, and non-coding RNAs. Compounds like EGCG and ellagic acid have been shown to restore the expression of tumor suppressor genes. Special attention is given to different types of breast cancer, especially triple-negative breast cancer (TNBC), which currently has limited treatment options and poor outcomes. Laboratory studies suggest that plant-based compounds can enhance the sensitivity of TNBC cells to standard chemotherapy, while also impacting immune and metabolic functions. Advances in nanotechnology, such as liposome-encapsulated curcumin, gold nanoparticles containing berberine, and nano-delivery systems for resveratrol, have improved the absorption and effectiveness of these substances. In conclusion, natural compounds represent a valuable source of novel therapeutics for breast cancer management, bridging molecular insights with translational potential.

乳腺癌（BC）是最常见的癌症，也是全世界妇女癌症相关死亡的主要原因。其显著的分子异质性导致不同的应答率，使标准治疗方法相对无效。最近的证据强调了以天然化合物为基础的疗法在调节致癌信号、调节表观遗传机制和重塑肿瘤微环境方面的前景。本文系统探讨了姜黄素、白藜芦醇、百里醌和小檗碱等生物活性植物化学物质在BC中的抗癌潜力。这些药物表现出多效性机制，如促进细胞凋亡（如通过p53激活）、抑制血管生成（如通过VEGF下调）和逆转化疗耐药（如通过抑制PI3K/AKT/mTOR轴）。探讨了表观遗传调控的作用，重点是DNA甲基化，组蛋白修饰和非编码rna。EGCG和鞣花酸等化合物已被证明可以恢复肿瘤抑制基因的表达。特别关注不同类型的乳腺癌，特别是三阴性乳腺癌（TNBC），目前治疗选择有限，结果不佳。实验室研究表明，基于植物的化合物可以增强TNBC细胞对标准化疗的敏感性，同时也会影响免疫和代谢功能。纳米技术的进步，如脂质体封装的姜黄素、含有小檗碱的金纳米颗粒和白藜芦醇的纳米递送系统，已经改善了这些物质的吸收和有效性。总之，天然化合物代表了乳腺癌治疗新疗法的宝贵来源，将分子见解与转化潜力联系起来。

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引用次数: 0

Unraveling ADC resistance in hematologic malignancies: Challenges and new frontiers 揭示ADC在血液恶性肿瘤中的耐药性：挑战和新领域。

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2026-02-01 Epub Date: 2025-12-22 DOI: 10.1016/j.prp.2025.156341

Monica Armanious, Farida K. Gebreel, Reem W. Algendy, Rahma Hefny, Amira M. Ismail, Patrick M. Maximous, Hend M. El Tayebi

Antibody-drug conjugates (ADCs) initiated a pivotal therapeutic strategy in hematologic malignancies, by combining targeted cytotoxicity with high specificity and reduced systemic toxicity. However, despite promising clinical outcomes, resistance to ADCs raises a remarkable challenge, limiting their long-term efficacy. This review explored the multiplex mechanisms underlying ADC resistance emerging in different hematologic cancers, including overexpression of drug efflux pumps, antigen loss or downregulation, impaired intracellular trafficking, and altered apoptotic pathways. The review sheds the light on the role of tumor microenvironment in promoting resistance and hindering the ultimate ADCs efficacy as well as emerging strategies to overcome resistance such as combination therapies, next-generation ADCs, and biomarker-driven patient selection. Understanding the molecular basis of ADC resistance is crucial for optimizing treatment regimens and guiding future therapeutic development in hematologic malignancies.

抗体-药物偶联物（adc）通过结合高特异性的靶向细胞毒性和降低全身毒性，开创了血液系统恶性肿瘤的关键治疗策略。然而，尽管有很好的临床结果，对adc的耐药性提出了显著的挑战，限制了它们的长期疗效。这篇综述探讨了不同血液学癌症中ADC耐药的多重机制，包括药物外排泵的过表达、抗原丢失或下调、细胞内运输受损以及凋亡途径的改变。这篇综述揭示了肿瘤微环境在促进耐药和阻碍adc最终疗效方面的作用，以及克服耐药的新策略，如联合治疗、下一代adc和生物标志物驱动的患者选择。了解ADC耐药的分子基础对于优化治疗方案和指导未来血液恶性肿瘤的治疗发展至关重要。

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引用次数: 0

Acute myeloid leukemia with plasmacytoid dendritic cell differentiation initially presenting as skin lesions: A case report 急性髓系白血病伴浆细胞样树突状细胞分化，最初表现为皮肤病变：1例报告。

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2026-02-01 Epub Date: 2025-12-05 DOI: 10.1016/j.prp.2025.156324

Chenxi Xiang , Shaoqi Li , Jia Liu , Qianqian Yin , Dongshen Ma , Hui Liu

Plasmacytoid dendritic cell (pDC) accumulations are frequently observed in association with myeloid neoplasms in the bone marrow. We report a case diagnosed as acute myeloid leukemia (AML) with pDC differentiation, which first presented as skin lesions and lymphadenopathies. The skin biopsy revealed pDC-like cells infiltrating the dermal layer. The architecture of the cervical lymph node remained largely preserved, but it was infiltrated by monotonous, atypical cells with a pDC-like immunophenotype in the interfollicular areas. Flow cytometry analysis of the lymph node tissue confirmed the heterogeneity and pDC-like immunophenotype of the tumor cells. Furthermore, a bone marrow biopsy confirmed the presence of underlying AML. DNA sequencing demonstrated that the tumor cells in both the tumor cells in the lymph node and skin biopsy shared the identical genetic abberations as in the bone marrow. Based on these findings, a diagnosis of AML with pDC differentiation was established.

浆细胞样树突状细胞（pDC）的积累经常被观察到与骨髓中的髓系肿瘤有关。我们报告一例诊断为急性髓性白血病（AML）与pDC分化，首先表现为皮肤病变和淋巴结病变。皮肤活检显示pdc样细胞浸润真皮层。颈部淋巴结的结构基本保留，但在滤泡间区浸润了单调的非典型细胞，具有pdc样免疫表型。淋巴组织的流式细胞术分析证实了肿瘤细胞的异质性和pdc样免疫表型。此外，骨髓活检证实存在潜在的AML。DNA测序表明，淋巴结和皮肤活检中的肿瘤细胞与骨髓中的肿瘤细胞具有相同的遗传畸变。基于这些发现，AML伴pDC分化的诊断得以确立。

引用次数: 0

LDH-driven lactic acidosis in hypoxic solid tumors: Mechanisms of metastatic transformation and therapeutic opportunities 低氧实体瘤中ldh驱动的乳酸酸中毒：转移转化机制和治疗机会

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2026-02-01 Epub Date: 2025-12-25 DOI: 10.1016/j.prp.2025.156342

Priyanshu Kumar , Saumya Rastogi , Mandeep Kumar Arora , Lakhveer Singh

Lactic acidosis is a characteristic feature of solid hypoxic cancerous tumors, those that develop in the breast, colon, and prostate tissue. Even though extreme lactic acidosis is damaging to healthy cells, malignant tumors actually benefit from it in several different ways. Lactic acidosis in TME (TME) imparts resistance to chemotherapy and helps them from immune invasion. Lactic acidosis further benefits the tumor cells by inducing the formation of new blood vessels. Acidic tumour microenvironment (TME) provides very favourable pH conditions for activation of proteolytic enzymes like Matrix metalloproteinase (MMP-2/9), which helps the tumor cells invade into the nearby organs. Because aggressive hypoxic cancer cells have a high chance of metastasising to other organs, it is difficult to manage a tumor at this stage with chemotherapy. Stopping hypoxia-induced Lactate dehydrogenase (LDH) from working can prevent cancers from behaving aggressively. Restraining lactate circulation in the TME by inhibiting LDH and its transporters i.e Monocarboxylate transporters (MCT-1/2) would be a promising therapeutic strategy to prevent metastatic transformation of solid hypoxic tumors. Moreover, nanotechnology can be implicated in various ways to selectively kill the cancer cells. Whereas in some cancers, chemotherapeutic agents fail to activate, pH-sensitive nanoparticles can be designed to target such cancer cells. In the current review, we have highlighted the role and mechanisms of lactic acidosis to transform the benign tumours into more aggressive metastatic tumors. This review also offers fresh perspectives on the variety of LDH and MCT inhibitors currently undergoing clinical trials to act in the acidic TME.

乳酸性酸中毒是发生于乳腺、结肠和前列腺组织的实性缺氧癌性肿瘤的特征。尽管极度乳酸性酸中毒对健康细胞是有害的，但恶性肿瘤实际上以几种不同的方式从中受益。乳酸性酸中毒（TME）赋予TME对化疗的抵抗力，帮助其抵抗免疫入侵。乳酸酸中毒通过诱导新血管的形成进一步有利于肿瘤细胞。酸性肿瘤微环境（TME）为基质金属蛋白酶（MMP-2/9）等蛋白水解酶的激活提供了非常有利的pH条件，从而帮助肿瘤细胞侵入附近器官。由于侵袭性缺氧癌细胞有很高的机会转移到其他器官，因此很难用化疗来控制这个阶段的肿瘤。停止缺氧诱导的乳酸脱氢酶（LDH）的工作可以防止癌症的侵袭性行为。通过抑制LDH及其转运体，即单羧酸转运体（MCT-1/2）来抑制TME中的乳酸循环可能是一种很有前途的治疗策略，可以防止实体缺氧肿瘤的转移转化。此外，纳米技术可以通过多种方式选择性地杀死癌细胞。然而在某些癌症中，化疗药物无法激活，因此可以设计ph敏感纳米颗粒来靶向这些癌细胞。在当前的综述中，我们强调了乳酸酸中毒在将良性肿瘤转化为更具侵袭性的转移性肿瘤中的作用和机制。本综述还为目前正在进行临床试验的各种LDH和MCT抑制剂在酸性TME中的作用提供了新的视角。

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引用次数: 0

Deciphering the role of angiogenesis in glioblastoma: Integrative insights from transcriptomic profiling, single-cell sequencing and interpretable machine learning approaches 解读血管生成在胶质母细胞瘤中的作用：来自转录组分析、单细胞测序和可解释的机器学习方法的综合见解。

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2026-02-01 Epub Date: 2025-11-24 DOI: 10.1016/j.prp.2025.156305

Fan Yang , Chi Peng , Sisi Yang , Xiuwu Bian , Xiaohong Yao

Glioblastoma (GBM), a highly vascularized and aggressive primary brain tumor, presents unresolved questions regarding the functional significance of angiogenesis-related genes (ARGs) in disease progression. To systematically investigate this, we employed univariate Cox regression followed by LASSO regression analysis to identify prognosis-associated ARGs. These candidates were subsequently evaluated using six machine learning-derived survival prediction algorithms, with model interpretability achieved through SHapley Additive exPlanations (SHAP) analysis. Our studies revealed that six hub ARGs (BMP2, FSCN1, NET1, AEBP1, SEMA3G, and RAB37) were identified and incorporated into a novel risk stratification model (high and low risk groups). High-risk patients demonstrated significantly poorer overall survival in the CGGA-GBM, GSE43378, and GSE7696 cohorts. Moreover, the high-risk group exhibited an immunosuppressive tumor microenvironment profile (e.g., elevated Treg infiltration, P < 0.0001), increased extracellular matrix stiffness (via mechanosensing markers) and differential drug sensitivity (OncoPredict analysis). Immunofluorescence confirmed co-localization of the hub protein FSCN1 with vascular (CD31⁺), stromal (α-SMA⁺), and mesenchymal (Vimentin⁺) compartments, suggesting its multifunctional role in GBM pathobiology. In summary, our research established the ARG-derived prognostic signature validated across independent GBM cohorts and revealed concomitant immune and mechanical niche dysregulation in high-risk patients. The rationale for combined angiogenesis/stroma/immune modulation strategies was provided, with FSCN1 proposed as the potential therapeutic target.

胶质母细胞瘤（GBM）是一种高度血管化和侵袭性的原发性脑肿瘤，关于血管生成相关基因（ARGs）在疾病进展中的功能意义提出了尚未解决的问题。为了系统地研究这一点，我们采用单变量Cox回归和LASSO回归分析来确定与预后相关的ARGs。随后使用六种机器学习衍生的生存预测算法对这些候选者进行评估，并通过SHapley加性解释（SHAP）分析实现模型的可解释性。我们的研究发现，6个枢纽ARGs （BMP2、FSCN1、NET1、AEBP1、SEMA3G和RAB37）被确定并纳入了一个新的风险分层模型（高风险组和低风险组）。高危患者在CGGA-GBM、GSE43378和GSE7696队列中表现出明显较差的总生存率。此外，高危组表现出免疫抑制的肿瘤微环境特征(如Treg浸润升高，P

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引用次数: 0

Harnessing the therapeutic potential of TIMP-1 in autoimmune inflammation: A prospective insight 利用TIMP-1在自身免疫性炎症中的治疗潜力：一个前瞻性的见解。

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2026-02-01 Epub Date: 2025-12-16 DOI: 10.1016/j.prp.2025.156334

Shangomitra Bhattacharjee, Mahaboobkhan Rasool

Tissue inhibitors of matrix metalloproteinase 1 (TIMP-1) have recently attracted significant attention owing to their newly discovered cytokine function. These findings prompted a reevaluation of TIMP-1's role as an inhibitor of matrix metalloproteinase. Elevated TIMP-1 levels have been observed in various autoimmune conditions, influencing disease outcomes in multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. Furthermore, TIMP-1 affects context-dependent metabolic profiles, enhances glycolytic turnover in monocytes, and is associated with ferroptosis in patients with rheumatoid arthritis. TIMP-1 also supports MHC-I expression and CD8 + T-cell activation, indicating a more active role in autoimmune conditions. Considering the expanding body of knowledge regarding TIMP-1 and its significant role in modifying metabolic profiles and disease outcomes, we carefully reviewed the contrasting functions of TIMP-1. Additionally, we summarize the upstream activators and signaling pathways involved in TIMP-1 activation and its reciprocal effects. Although TIMP-1 expression is linked to diverse disease outcomes, it is advisable to adopt a more nuanced approach to utilizing TIMP-1 depending on the specific disease context. This review proposes various strategies for targeting TIMP-1 as a therapeutic intervention to modulate the outcomes of autoimmune disorders.

基质金属蛋白酶1 （TIMP-1）的组织抑制剂因其新发现的细胞因子功能而受到广泛关注。这些发现促使人们重新评估TIMP-1作为基质金属蛋白酶抑制剂的作用。在多种自身免疫性疾病中观察到TIMP-1水平升高，影响多发性硬化症、炎症性肠病和类风湿性关节炎的疾病结局。此外，TIMP-1影响环境依赖的代谢谱，增强单核细胞的糖酵解转换，并与类风湿关节炎患者的铁下垂有关。TIMP-1还支持MHC-I表达和CD8 + t细胞活化，表明在自身免疫性疾病中发挥更积极的作用。考虑到有关TIMP-1及其在改变代谢谱和疾病结局中的重要作用的知识体系不断扩大，我们仔细回顾了TIMP-1的对比功能。此外，我们总结了上游激活因子和参与TIMP-1激活的信号通路及其相互作用。尽管TIMP-1的表达与多种疾病结果有关，但根据具体的疾病背景，采用更细致的方法来利用TIMP-1是可取的。这篇综述提出了针对TIMP-1的各种策略，作为一种治疗干预来调节自身免疫性疾病的结果。

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引用次数: 0

Unveiling the role of PGCCs in tumor recurrence and therapeutic resistance: Hidden architects of cancer’s comeback 揭示PGCCs在肿瘤复发和治疗耐药中的作用：癌症复发的隐藏建筑师

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2026-02-01 Epub Date: 2025-12-29 DOI: 10.1016/j.prp.2025.156347

Mokhtar Rejili , Farid Hashemi

Polyploid Giant Cancer Cell (PGCCs) have emerged as pivotal players in cancer biology, contributing to tumor heterogeneity, recurrence, metastasis, and resistance to conventional therapies. Characterized by their enlarged size, aberrant nuclear morphology, and stem-like properties, PGCCs arise in response to environmental stressors such as chemotherapy, radiation, and hypoxia. These cells enter a dormant state, evade treatment, and later become reactivated to generate tumor-repopulating progeny through depolyploidization and asymmetric division (neosis). Daughter cells derived from PGCCs exhibit enhanced invasive capabilities, epithelial-to-mesenchymal transition (EMT), and metabolic adaptability, rendering PGCCs formidable obstacles in cancer management. Their unique biology involves complex molecular mechanisms including endoreplication, cell fusion, and autophagy, which facilitate survival and proliferation under stress conditions. Elucidating PGCC formation and behavior opens new avenues for targeted therapeutic strategies, encompassing immunomodulation, metabolic interference, and differentiation-based approaches. This paradigm shift in cancer research underscores the urgency for innovative diagnostic tools and personalized treatment modalities to effectively counter PGCC-driven malignancies.

多倍体巨癌细胞（Polyploid Giant Cancer Cell, PGCCs）在癌症生物学中扮演着关键角色，对肿瘤的异质性、复发、转移和对常规治疗的耐药性起着重要作用。pgcc的特点是体积增大、核形态异常和茎样性质，是对环境应激因素（如化疗、放疗和缺氧）的反应。这些细胞进入休眠状态，逃避治疗，然后重新激活，通过去多倍体和不对称分裂（新生）产生肿瘤再生的后代。pgcc衍生的子细胞表现出增强的侵袭能力、上皮-间质转化（EMT）和代谢适应性，使pgcc在癌症治疗中成为巨大的障碍。它们独特的生物学涉及复杂的分子机制，包括内复制、细胞融合和自噬，这些机制促进了应激条件下的生存和增殖。阐明PGCC的形成和行为为靶向治疗策略开辟了新的途径，包括免疫调节、代谢干扰和基于分化的方法。癌症研究的这种范式转变强调了创新诊断工具和个性化治疗方式的紧迫性，以有效对抗pgcc驱动的恶性肿瘤。

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引用次数: 0