Pathology, research and practice最新文献_第5页

Asiaticoside enhances the anti-tumor effect of anti-PDL1 by regulating T cell activity through increasing LCK activity 积雪草苷通过提高LCK活性来调节T细胞活性，从而增强抗pdl1的抗肿瘤作用

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-05-06 DOI: 10.1016/j.prp.2025.155995

Qingyi Ren , Fang Wang , Fei Du , Chenxi He , Xiaodong Wang , Jun Wang , Zhuo Zhang , Yuhong Sun

{"title":"Asiaticoside enhances the anti-tumor effect of anti-PDL1 by regulating T cell activity through increasing LCK activity","authors":"Qingyi Ren , Fang Wang , Fei Du , Chenxi He , Xiaodong Wang , Jun Wang , Zhuo Zhang , Yuhong Sun","doi":"10.1016/j.prp.2025.155995","DOIUrl":"10.1016/j.prp.2025.155995","url":null,"abstract":"<div><div>Anti-PD-L1 antibody confers anti-tumor effects, but its long-term use can provoke resistance and adverse effects. Asiaticoside, a bioactive triterpene glycoside from <em>Centella asiatica</em> L., regulates immune function and induces apoptosis of hepatocellular carcinoma (HCC) cells. T cells play a vital role in killing tumor cells and require lymphocyte-specific protein tyrosine kinase (LCK) for activation. Here, we examined whether a combined asiaticoside and anti-PD-L1 treatment regulates T cells via LCK activation to enhance the anti-tumor effect in vivo. We established a subcutaneous mouse HCC model using Hepa1–6 cells and measured spleen and tumor weight. Morphological changes of tumor tissues were assessed by hematoxylin-eosin staining. Tumor cell apoptosis and proliferation were determined by TUNEL staining and KI67 immunohistochemistry. The proportion of activated T cells in the spleen was detected by flow cytometry, and the levels of phosphorylated p-LCK and p-AKT in the spleen were determined by Western blotting. Changes in the levels of serum inflammatory factors were detected with ELISA. Our results revealed that the combined asiaticoside and anti-PD-L1 treatment inhibited tumor growth by enhancing apoptosis and reducing tumor cell proliferation. The treatment activated T cells to increase the proportion of effector T cells in the spleen, evidenced by upregulated p-LCK and p-AKT levels. It also increased the level of TNF-α in the serum and decreased IL-6, implying an enhanced immune response. In conclusion, the combined asiaticoside and anti-PD-L1 treatment enhances the anti-HCC effect in vivo by promoting LCK activation to regulate T cells.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"271 ","pages":"Article 155995"},"PeriodicalIF":2.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of NCOA4-mediated ferritinophagy in the ferroptosis of hepatocytes: A mechanistic viewpoint ncoa4介导的铁蛋白自噬在肝细胞铁凋亡中的作用：一个机制观点

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-05-06 DOI: 10.1016/j.prp.2025.155996

Huixian Zhao , Zhixin Wang , Haijiu Wang

{"title":"The role of NCOA4-mediated ferritinophagy in the ferroptosis of hepatocytes: A mechanistic viewpoint","authors":"Huixian Zhao , Zhixin Wang , Haijiu Wang","doi":"10.1016/j.prp.2025.155996","DOIUrl":"10.1016/j.prp.2025.155996","url":null,"abstract":"<div><div>This paper focuses on the mechanism underlying nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and subsequent hepatocyte ferroptosis. Iron is a pivotal trace element, but excessive iron deposition can lead to liver injury. Ferroptosis is a recognized, iron-dependent mode of programmed cell death that plays an important role in various liver diseases. NCOA4 is a key molecule mediating the selective autophagic degradation of ferritin. It affects ferroptosis by regulating intracellular free iron levels. NCOA4 expression is regulated by various factors, including cellular iron levels and oxidative stress. It was demonstrated that inhibition of NCOA4 can reduce iron-mediated cell death and mitigate liver damage, suggesting that NCOA4 may be a potential target for the prevention and treatment of liver diseases. Further in-depth studies of the molecular mechanism of NCOA4-mediated ferritinophagy and its relationship with iron-induced cell death can provide novel ideas for the diagnosis and treatment of liver diseases. The deficiency or abnormal expression of NCOA4 is closely associated with ferroptosis in a variety of liver diseases, including non-alcoholic fatty liver disease, alcoholic liver disease, drug-induced liver injury, and liver fibrosis. Future studies should focus on elucidating the dynamic changes in the NCOA4 regulatory network during specific pathological processes. This strategy can lay the foundation for drug development.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155996"},"PeriodicalIF":2.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Infiltrating Natural Killer cells influence the efficacy of BCG immunotherapy in non-muscle-invasive bladder cancer 浸润性自然杀伤细胞影响卡介苗免疫治疗非肌浸润性膀胱癌的疗效

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-05-06 DOI: 10.1016/j.prp.2025.155997

Mariana Z.T. Lima , Diogo A. Bastos , Romulo L. Mattedi , Carlos Dzik , Denis L.F. Jardim , Rafael Coelho , Leopoldo A. Ribeiro-Filho , Maurício D. Cordeiro , William C. Nahas , Evandro S. Mello , Mariane T. Amano , Lilian T. Inoue , Anamaria A. Camargo

{"title":"Infiltrating Natural Killer cells influence the efficacy of BCG immunotherapy in non-muscle-invasive bladder cancer","authors":"Mariana Z.T. Lima , Diogo A. Bastos , Romulo L. Mattedi , Carlos Dzik , Denis L.F. Jardim , Rafael Coelho , Leopoldo A. Ribeiro-Filho , Maurício D. Cordeiro , William C. Nahas , Evandro S. Mello , Mariane T. Amano , Lilian T. Inoue , Anamaria A. Camargo","doi":"10.1016/j.prp.2025.155997","DOIUrl":"10.1016/j.prp.2025.155997","url":null,"abstract":"<div><div>Non-muscle-invasive bladder cancer (NMIBC) consists of tumors restricted to the bladder urothelium or lamina propria, without invasion of the muscular layer. Intravesical BCG (Bacillus Calmette-Guérin) is widely used as an adjuvant therapy for patients with intermediate or high-risk NMIBC. However, a significant proportion of these patients fail to respond to BCG or recur after treatment. Moreover, despite decades of BCG usage, there are still no clinically validated biomarkers capable of predicting which patients will benefit from this treatment. Emerging evidence suggests that the tumor immune microenvironment influences the efficacy of BCG immunotherapy. In this context, our study aimed to assess, by immunohistochemistry, whether the abundance of immune cell subpopulations – Natural Killer (NK) cells, tumor-associated macrophages (TAMs), CD4 + T, CD8 + T, and FOXP3 + regulatory T (Treg) cells, or T cell ratios (CD4 +/CD8 + and FOXP3 +/CD8 +) – in NMIBC urothelium, prior to BCG, were associated with BCG response rate (RR) and recurrence-free survival (RFS) after treatment. We demonstrated that higher pretreatment NK cell count in the NMIBC urothelium is significantly associated with improved BCG RR and prolonged RFS after BCG immunotherapy. We hypothesize these results are associated with BCG-induced trained immunity, which has been proposed to be essential for the efficacy of BCG immunotherapy in bladder cancer. Once validated and further investigated by future studies, our findings may help to improve the stratification and treatment of patients with NMIBC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155997"},"PeriodicalIF":2.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

USP46 regulates glycolysis in the process of cardiac hypertrophy through the HIF-1α pathway USP46通过HIF-1α途径调控心肌肥厚过程中的糖酵解

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-29 DOI: 10.1016/j.prp.2025.155980

Chunling Mu , Dahai Yu , Aixin Li , Yang Yu , Zhaoguang Liang

{"title":"USP46 regulates glycolysis in the process of cardiac hypertrophy through the HIF-1α pathway","authors":"Chunling Mu , Dahai Yu , Aixin Li , Yang Yu , Zhaoguang Liang","doi":"10.1016/j.prp.2025.155980","DOIUrl":"10.1016/j.prp.2025.155980","url":null,"abstract":"<div><div>Cardiac hypertrophy, a hallmark of various cardiovascular diseases, is characterized by metabolic reprogramming that leads to enhanced glycolytic activity. In the present study, we aimed to investigate the role of ubiquitin-specific protease46 (USP46) in regulating glycolysis of cardiac hypertrophy through the HIF-1α pathway. We provided evidence that USP46 was significantly elevated in hypertrophied mouse heart and in cell hypertrophy model, correlating with increased HIF-1α stability and activation of downstream glycolytic enzymes. We observed that knockdown of USP46 led to decreased HIF-1α levels and reduction in glycolysis rate, thereby attenuating myocardial hypertrophy in mice model of cardiac hypertrophy. Conversely, overexpression of USP46 enhanced the expression of HIF-1α, leading to increased glycolytic activity and exacerbation of cardiac hypertrophy. In vitro studies further demonstrated that USP46 enhances the stability of HIF-1α by binding to HIF-1α and reducing the ubiquitination of HIF-1α, thus promotes the transcriptional activity of HIF-1α, eventually facilitating the expression of metabolic genes associated with glycolysis. Metabolic profiling also confirmed that USP46/HIF-1α intervention significantly influenced lactate, pyruvate and ATP production in cardiac myocytes. Collectively, our findings suggest that USP46 plays a pivotal role in cardiac hypertrophy by modulating HIF-1α-dependent glycolytic processes. This study positions USP46 as a promising therapeutic target for the management of cardiac hypertrophy and related cardiovascular diseases, offering insights into the intricate interplay between deubiquitination, glycolysis, and cardiac remodeling.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155980"},"PeriodicalIF":2.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From blockage to biology: Unveiling the role of extracellular matrix dynamics in obstructive colorectal cancer pathogenesis 从阻塞到生物学：揭示细胞外基质动力学在梗阻性结直肠癌发病机制中的作用

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-28 DOI: 10.1016/j.prp.2025.155994

Jun Wang , Mian Chen , Guanxin Wei , Falong Zou , Junnan Gu , Yinghao Cao , Shenghe Deng , Kailin Cai

{"title":"From blockage to biology: Unveiling the role of extracellular matrix dynamics in obstructive colorectal cancer pathogenesis","authors":"Jun Wang , Mian Chen , Guanxin Wei , Falong Zou , Junnan Gu , Yinghao Cao , Shenghe Deng , Kailin Cai","doi":"10.1016/j.prp.2025.155994","DOIUrl":"10.1016/j.prp.2025.155994","url":null,"abstract":"<div><div>Colorectal cancer obstruction is a common problem with distinct symptomatic clues on CT/MR images even under incomplete conditions. The choice of management in the emergency setting has a significant effect on the prognosis of obstructive and nonobstructive colorectal cancer patients. Previous studies have demonstrated that obstruction in colorectal cancer is associated with significantly poorer outcomes, alongside distinct alterations in the composition of the extracellular matrix. Based on accumulating evidence, it is hypothesized that ECM remodeling plays a pivotal role in the development of colorectal cancer obstruction. This review explores the pathological features of obstructive colorectal cancer, emphasizing extracellular matrix remodeling as a central process. Key mechanisms include tumor-stromal cell interactions, tumor cell aggregation and migration mediated by the peripheral nervous system, vascular and lymphatic remodeling within the tumor microenvironment, and microbiota-mediated regulation of cancer progression. These findings demonstrate that further remodeling of the extracellular matrix may be a molecular biological feature of obstructive colorectal cancer with poor prognosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155994"},"PeriodicalIF":2.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EZH2 regulatory roles in cancer immunity and immunotherapy EZH2在肿瘤免疫和免疫治疗中的调节作用

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-28 DOI: 10.1016/j.prp.2025.155992

Keywan Mortezaee

{"title":"EZH2 regulatory roles in cancer immunity and immunotherapy","authors":"Keywan Mortezaee","doi":"10.1016/j.prp.2025.155992","DOIUrl":"10.1016/j.prp.2025.155992","url":null,"abstract":"<div><div>Enhancer of zeste homolog 2 (EZH2) is a polycomb repressor complex 2 (PRC2) subunit that is responsible for silencing expression of target genes through generation of lysine 27 trimethylation on histone H3 (H3K27Me3). EZH2 is an oncogene aberrantly expressed in human cancers, and its overexpression favors immune escape and metastasis. Immune escape occurs via the impact of EZH2 on hampering antigen expression machinery, stabilizing FOXP3 in regulatory T cells (Tregs), inhibiting recruitment and activity of natural killer (NK) and CD8<sup>+</sup> T cells, and inducing recruitment and activity of myeloid-derived suppressor cells (MDSCs). Besides, EZH2 also promotes intra-tumoral recruitment of tumor-associated macrophages (TAMs). A point is that pharmacologic EZH2 inhibition (not knockdown) seemingly promotes polarization of macrophages toward pro-tumor M2 phenotype, which defines resistance mechanism. Besides, increased EZH2 expression after anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and a rise in the tumoral expression of programmed death-ligand 1 (PD-L1) after EZH2 inhibition account for secondary immunosuppression in tumor ecosystem after immunotherapy, indicating the applicability of using EZH2 targeted therapies as a combinatory approach with anti-programmed death-1 (PD-1) or anti-CTLA-4 therapy. Such combination reinvigorates anti-tumor immunity and presumably hampers T cell exhaustion and acting as a promising regimen for retarding cancer growth.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155992"},"PeriodicalIF":2.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The combined diagnostic value of 5-hmC and PRAME immunohistochemistry in melanocytic neoplasms 5-hmC与PRAME免疫组化在黑色素细胞肿瘤中的联合诊断价值

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-27 DOI: 10.1016/j.prp.2025.155993

Yanhong Yu , Niloufar Hosseini , David Dodington , Kimberly Wood , Danny Ghazarian , Zaid Saeed Kamil

{"title":"The combined diagnostic value of 5-hmC and PRAME immunohistochemistry in melanocytic neoplasms","authors":"Yanhong Yu , Niloufar Hosseini , David Dodington , Kimberly Wood , Danny Ghazarian , Zaid Saeed Kamil","doi":"10.1016/j.prp.2025.155993","DOIUrl":"10.1016/j.prp.2025.155993","url":null,"abstract":"<div><div>The diagnosis of melanocytic neoplasms, particularly those with borderline morphologic features, remains a challenging area in dermatopathology. 5-hydroxymethylcytosine (5-hmC) and PRAME (PReferentially expressed Antigen in MElanoma) are recent immunohistochemical markers which have been shown to be valuable in distinguishing benign from malignant melanocytic neoplasms. A retrospective cohort of 144 benign, borderline (Spitz nevi, atypical Spitz tumors and dysplastic nevi) and malignant melanocytic tumors at our institution were analyzed for 5-hmC and PRAME expression by immunohistochemistry. Compared to benign nevi, melanoma cases had higher PRAME expression (p < 0.0001) and lower 5-hmC (p < 0.0001) expression. In receiver operator curve analysis, 5-hmC and PRAME were good discriminators between benign and malignant neoplasms; the area under the curve (AUC) was 0.91 for 5-hmC (p < 0.0001) and 0.94 for PRAME (p < 0.001). Subgroup analysis showed that 5-hmC expression was significantly different between dysplastic nevi and melanoma. The combination of PRAME and 5-hmC significantly improved the predictive ability of these markers (AUC 0.97, p < 0.001). Having both PRAME expression of 4 + (> 75 % lesional cells positive) and 5-hmC of < 0.2 was highly specific for malignancy (98 %) with a sensitivity of 61 %. Utilizing 5-hmC and PRAME in conjunction improves their diagnostic value in distinguishing benign from malignant melanocytic neoplasms.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155993"},"PeriodicalIF":2.9,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The clinicopathological characteristics of co-mutations in exon 2 and 3 of the KRAS gene in patients with colorectal cancer 结直肠癌患者KRAS基因外显子2、3共突变的临床病理特征

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-24 DOI: 10.1016/j.prp.2025.155990

Huizhen Peng, Hongtian Yao, Xiaojun Jiang, Huijuan Zhu, Jun Li, Hui Tang

{"title":"The clinicopathological characteristics of co-mutations in exon 2 and 3 of the KRAS gene in patients with colorectal cancer","authors":"Huizhen Peng, Hongtian Yao, Xiaojun Jiang, Huijuan Zhu, Jun Li, Hui Tang","doi":"10.1016/j.prp.2025.155990","DOIUrl":"10.1016/j.prp.2025.155990","url":null,"abstract":"<div><div><em>KRAS,</em> one of the most frequently mutated oncogenes in colorectal cancer (CRC), with mutations in approximately 40 % of all CRC cases. <em>KRAS</em> mutations exhibit considerable diversity. Studies have shown that patients with mutations at codon 13 (G13) of the <em>KRAS</em> gene have a higher risk of mortality, while mutations at codon 12 (G12) of the <em>KRAS</em> gene are also associated with prognosis, though their impact on mortality risk is lower than that of codon 13 mutations. Therefore, identifying the specific <em>KRAS</em> mutation type is crucial for assessing patient prognosis and developing personalized treatment plans. <em>KRAS</em> mutations typically occur in a single exon, whereas co-mutations in exon 2 (G12/G13) and exon 3 (Q61) in a single tissue haven’t been reported yet. In this study, we reported a co-mutation in two exons (exon 2 and exon 3) of the <em>KRAS</em> gene in a 72-year-old male with CRC, adenocarcinoma located at 8 cm from the anus. NGS and ARMS-PCR revealed that two exons of <em>KRAS</em> were co-mutated in this patient-- Q61H in exon 3, with a mutation frequency of 21.09 % and G13D in exon 2, with a variance frequency of 6.06 %. A copy number increase (copy number: 5.65) in <em>MET</em> gene was also found in this patient simultaneously. The clinicopathological characteristics were analyzed, and the possible mechanisms were further discussed. However, due to the CRC patients with co-mutations in two exons of the <em>KRAS</em> are exceedingly rare, a cohort study with more patients’ clinical data is urged.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155990"},"PeriodicalIF":2.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Defining molecular signatures of the solid/pseudopapillary and pseudoglandular patterns in so-called “solid-tubulocystic intrahepatic cholangiocarcinoma vs. NIPBL::NACC1 fusion hepatic carcinoma” 在所谓的“固体小管囊性肝内胆管癌与NIPBL::NACC1融合肝癌”中定义实性/假乳头状和假腺状模式的分子特征

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-23 DOI: 10.1016/j.prp.2025.155962

Prachi Bajpai , Fatme Ghandour , Ekta Jain , Raima Memon , Chirag R. Patel , Santhosh Kumar Karthikeyan , Sankarasubramanian Jagadesan , Babu Guda , Farrukh Afaq , Amr Elkholy , Sooryanarayana Varambally , Upender Manne , Sameer Al Diffalha

{"title":"Defining molecular signatures of the solid/pseudopapillary and pseudoglandular patterns in so-called “solid-tubulocystic intrahepatic cholangiocarcinoma vs. NIPBL::NACC1 fusion hepatic carcinoma”","authors":"Prachi Bajpai , Fatme Ghandour , Ekta Jain , Raima Memon , Chirag R. Patel , Santhosh Kumar Karthikeyan , Sankarasubramanian Jagadesan , Babu Guda , Farrukh Afaq , Amr Elkholy , Sooryanarayana Varambally , Upender Manne , Sameer Al Diffalha","doi":"10.1016/j.prp.2025.155962","DOIUrl":"10.1016/j.prp.2025.155962","url":null,"abstract":"<div><div>Solid-tubulocystic variant of intrahepatic cholangiocarcinoma (ST-iCCA) is newly described entity characterized by two distinct histologic growth patterns: (1) solid sheets of tumor cells with focal necrosis giving pseudopapillary appearance and (2) tubular or pseudoglandular structures containing pink, colloid-like material. Tumor cells are inhibin-positive and harbor <em>NIPBL::NACC1</em> fusion gene. To date, only 28 cases of ST-iCCA have been documented. While prior molecular studies provided insights into ST-iCCA, genetic profiles of individual histologic components have not been explored. This study presents first transcriptomic analysis comparing the solid/pseudopapillary and pseudoglandular components of ST-iCCA. Two cases of histologically confirmed ST-iCCA were identified for RNA sequencing which was performed on solid/pseudopapillary component, pseudoglandular component, and normal tissue. Analysis revealed distinct gene expression profiles for each pattern. Solid/pseudopapillary component uniquely overexpressed <em>DMRTA1, NEXMIF, PRDM6, SORCS3,</em> and <em>NALF,</em> while pseudoglandular component exhibited unique overexpression of HRG<em>, ITIH3, TAT, APOA2, CP, ALDOB, CPS1, F2, KHG1, SERPINC1, HPX, C9, ADGRF1, MUC21, SAA2, SPRR2A, SAA1, FGL1, CFHR1,</em> and <em>LBP.</em> These findings establish unique gene signatures for these variants of ST-iCCA, providing potential biomarkers for differential diagnosis, prognosis and targeted therapy. The distinct genetic profiles may also uncover novel therapeutic targets to address the aggressive nature of ST-iCCA.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155962"},"PeriodicalIF":2.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The critical role of GLP-1 signaling pathways in the pathology of Parkinson's disease and diabetes GLP-1信号通路在帕金森病和糖尿病病理中的关键作用

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-22 DOI: 10.1016/j.prp.2025.155985

Jinhao Chen , Xiang Dong , Yichen Lin , Cunming Lv

{"title":"The critical role of GLP-1 signaling pathways in the pathology of Parkinson's disease and diabetes","authors":"Jinhao Chen , Xiang Dong , Yichen Lin , Cunming Lv","doi":"10.1016/j.prp.2025.155985","DOIUrl":"10.1016/j.prp.2025.155985","url":null,"abstract":"<div><div>This review assesses the roles of GLP-1 and its receptor agonists (GLP-1RAs) in the treatment of diabetes and Parkinson’s disease, integrating current theories and research. GLP-1, a vital endogenous hormone, regulates insulin secretion, delays gastric emptying, and promotes satiety, showing significant potential for diabetes management. However, its brief lifespan and restricted blood-brain barrier penetration limit its clinical application. To overcome these constraints, researchers have developed GLP-1 receptor agonists that prolong its action and exhibit high efficacy in diabetes treatment. Recent studies further reveal GLP-1’s neuroprotective effects, notably its potential in managing neurodegenerative disorders such as Parkinson’s disease. GLP-1RAs mitigate neuroinflammation, reduce oxidative stress, and enhance neuroprotection, suggesting substantial potential for treating neurodegenerative diseases. Additionally, to enhance GLP-1RAs’ efficacy in the nervous system, researchers have introduced novel drug delivery approaches, including nanoparticle carriers and molecular modifications, to improve stability and targeting accuracy. In conclusion, this review comprehensively analyzes the mechanisms, clinical applications, and challenges of GLP-1 and its receptor agonists in managing diabetes and Parkinson’s disease, while identifying future research and clinical opportunities.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155985"},"PeriodicalIF":2.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0