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Prognostic Significance of Intratumoral and Peritumoral Budding in Distal Extrahepatic Bile Duct Carcinoma. 远端肝外胆管癌瘤内和瘤周萌发的预后意义
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-12-19 DOI: 10.1159/000535847
Sun-Young Jun, Seung-Mo Hong, Soyeon An
{"title":"Prognostic Significance of Intratumoral and Peritumoral Budding in Distal Extrahepatic Bile Duct Carcinoma.","authors":"Sun-Young Jun, Seung-Mo Hong, Soyeon An","doi":"10.1159/000535847","DOIUrl":"10.1159/000535847","url":null,"abstract":"<p><strong>Introduction: </strong>Although tumor budding (TB) has been recognized as a representative adverse prognosticator in gastrointestinal malignancies, it is not well elucidated in distal extrahepatic bile duct carcinoma (DBDC). Herein, we investigated the prognostic significance of peritumoral (PTB) and intratumoral (ITB) budding according to the modified DBDC staging of the 8th edition of the American Joint Committee on Cancer.</p><p><strong>Methods: </strong>PTB and ITB were independently evaluated in a cohort of DBDC patients (n = 410) based on the 2016 International Tumor Budding Consensus Conference.</p><p><strong>Results: </strong>High levels of PTB (PTBHigh, ≥ grade-2) and ITB (ITBHigh, ≥ grade-3) were identified in 316 (77%) and 238 (58%) cases, respectively. In univariate analysis, PTBHigh and ITBHigh, larger size and sclerosing tumor growth pattern, higher histologic grade, extrapancreatic location, adenocarcinomas unrelated to intraductal papillary neoplasm of the bile duct, pancreatic, duodenal, and lymphovascular invasion, perineural invasion, cancer involvement of the bile duct resection margin, nodal metastasis, and higher T and N categories and disease stages were associated with shorter patient overall survival (OS) times. In multivariate analysis, PTBHigh and ITBHigh remained poor independent prognostic indicators of OS in DBDC patients. Specifically, ITBHigh could predict poor prognosis in patients with stage I (T1N0) DBDC.</p><p><strong>Conclusions: </strong>Both PTBHigh and ITBHigh were strong prognostic indicators in patients with DBDC. Thus, ITB could be used to predict worse prognoses in patients with DBDC, in which PTB is difficult to assess, especially for patients with stage I (T1N0) DBDC.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"254-267"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Decreasing Albumin mRNA Expression in Cholangiocarcinomas along the Bile Duct Tree. 降低藻胆蛋白 mRNA 在胆囊导管中的表达。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2024-05-19 DOI: 10.1159/000538706
Elisa Albertini, Stefano Chillotti, Giada Monti, Deborah Malvi, Marzia Deserti, Alessio Degiovanni, Andrea Palloni, Simona Tavolari, Giovanni Brandi, Antonia D'Errico, Francesco Vasuri
{"title":"Decreasing Albumin mRNA Expression in Cholangiocarcinomas along the Bile Duct Tree.","authors":"Elisa Albertini, Stefano Chillotti, Giada Monti, Deborah Malvi, Marzia Deserti, Alessio Degiovanni, Andrea Palloni, Simona Tavolari, Giovanni Brandi, Antonia D'Errico, Francesco Vasuri","doi":"10.1159/000538706","DOIUrl":"10.1159/000538706","url":null,"abstract":"<p><strong>Introduction: </strong>The progressive technologies in albumin in situ hybridization (ISH) changed the routine application and the differential diagnosis of hepatic malignancies in the last years. The aim of the present work was to assess the diagnostic utility of albumin ISH on different cholangiocarcinoma (CCA) subtypes, as well as to assess how albumin production changes along the biliary tree.</p><p><strong>Methods: </strong>Forty-five CCAs were retrospectively selected: 29 intrahepatic (15 small-duct and 14 large-duct subtypes), 7 perihilar, and 9 extrahepatic. Histology was revised in all cases, and albumin ISH was automatically performed by the RNAscope®.</p><p><strong>Results: </strong>ISH was always negative in extrahepatic CCAs, only 1 perihilar case was positive, and any positivity was observed in 25/29 (86.2%) intrahepatic CCAs (p &lt; 0.001). Concerning CCA subtypes, mean cell positivity was 38.8 ± 29.8% in small-duct CCAs and 11.4 ± 21.9 in large-duct CCAs, respectively (p = 0.003); 12/15 (80.0%) small-duct and 3/14 (21.4%) large-duct CCAs showed &gt;5% positive cells (p = 0.002; odds ratio 14.7).</p><p><strong>Conclusions: </strong>The introduction of more sensitive techniques changed the indications for ISH since most small-duct intrahepatic CCAs show diffuse positivity. Albumin positivity decreases from liver periphery to the large ducts, suggesting that ISH can be helpful in the differential diagnosis between small-duct and large-duct CCAs, as well as between intrahepatic large-duct CCAs and metastases.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"338-344"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of Pleural Mesothelioma by Hierarchical Clustering Analyses Using Immune Cells within Tumor Microenvironment. 利用肿瘤微环境中的免疫细胞进行分层聚类分析,确定胸膜间皮瘤的特征。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2024-03-25 DOI: 10.1159/000538520
Shingo Inaguma, Chengbo Wang, Sunao Ito, Akane Ueki, Jerzy Lasota, Piotr Czapiewski, Renata Langfort, Janusz Rys, Joanna Szpor, Piotr Waloszczyk, Krzysztof Okoń, Wojciech Biernat, Shuji Takiguchi, David S Schrump, Markku Miettinen, Satoru Takahashi
{"title":"Characterization of Pleural Mesothelioma by Hierarchical Clustering Analyses Using Immune Cells within Tumor Microenvironment.","authors":"Shingo Inaguma, Chengbo Wang, Sunao Ito, Akane Ueki, Jerzy Lasota, Piotr Czapiewski, Renata Langfort, Janusz Rys, Joanna Szpor, Piotr Waloszczyk, Krzysztof Okoń, Wojciech Biernat, Shuji Takiguchi, David S Schrump, Markku Miettinen, Satoru Takahashi","doi":"10.1159/000538520","DOIUrl":"10.1159/000538520","url":null,"abstract":"<p><strong>Introduction: </strong>Over the past decade, classifications using immune cell infiltration have been applied to many types of tumors; however, mesotheliomas have been less frequently evaluated.</p><p><strong>Methods: </strong>In this study, 60 well-characterized pleural mesotheliomas (PMs) were evaluated immunohistochemically for the characteristics of immune cells within tumor microenvironment (TME) using 10 immunohistochemical markers: CD3, CD4, CD8, CD56, CD68, CD163, FOXP3, CD27, PD-1, and TIM-3. For further characterization of PMs, hierarchical clustering analyses using these 10 markers were performed.</p><p><strong>Results: </strong>Among the immune cell markers, CD3 (p &lt; 0.0001), CD4 (p = 0.0016), CD8 (p = 0.00094), CD163+ (p = 0.042), and FOXP3+ (p = 0.025) were significantly associated with an unfavorable clinical outcome. Immune checkpoint receptor expressions on tumor-infiltrating lymphocytes such as PD-1 (p = 0.050), CD27 (p = 0.014), and TIM-3 (p = 0.0098) were also associated with unfavorable survival. Hierarchical clustering analyses identified three groups showing specific characteristics and significant associations with patient survival (p = 0.016): the highest number of immune cells (ICHigh); the lowest number of immune cells, especially CD8+ and CD163+ cells (ICLow); and intermediate number of immune cells (ICInt). ICHigh tumors showed significantly higher expression of PD-L1 (p = 0.00038). Cox proportional hazard model identified ICHigh [hazard ratio (HR) = 2.90] and ICInt (HR = 2.97) as potential risk factors compared with ICLow. Tumor CD47 (HR = 2.36), tumor CD70 (HR = 3.04), and tumor PD-L1 (HR = 3.21) expressions were also identified as potential risk factors for PM patients.</p><p><strong>Conclusion: </strong>Our findings indicate immune checkpoint and/or immune cell-targeting therapies against CD70-CD27 and/or CD47-SIRPA axes may be applied for PM patients in combination with PD-L1-PD-1 targeting therapies in accordance with their tumor immune microenvironment characteristics.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"313-325"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288718","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
Comparison of Breast Fine-Needle Aspiration Cytology and Tissue Sampling for High-Throughput Proteomic Analysis and Cancer Biomarker Detection. 乳腺细针穿刺细胞学与组织取样在高通量蛋白质组分析和癌症生物标记物检测中的应用比较。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2024-05-31 DOI: 10.1159/000539478
Hye Eun Park, Dohyun Han, Jae Seok Lee, Ilias P Nikas, Hyeyoon Kim, Sohyeon Yang, Hyebin Lee, Han Suk Ryu
{"title":"Comparison of Breast Fine-Needle Aspiration Cytology and Tissue Sampling for High-Throughput Proteomic Analysis and Cancer Biomarker Detection.","authors":"Hye Eun Park, Dohyun Han, Jae Seok Lee, Ilias P Nikas, Hyeyoon Kim, Sohyeon Yang, Hyebin Lee, Han Suk Ryu","doi":"10.1159/000539478","DOIUrl":"10.1159/000539478","url":null,"abstract":"<p><strong>Introduction: </strong>Fine-needle aspiration cytology (FNAC) specimens are widely utilized for the diagnosis and molecular testing of various cancers. We performed a comparative proteomic analysis of three different sample types, including breast FNAC, core needle biopsy (CNB), and surgical resection tissues. Our goal was to evaluate the suitability of FNAC for in-depth proteomic analysis and for identifying potential therapeutic biomarkers in breast cancer.</p><p><strong>Methods: </strong>High-throughput proteomic analysis was conducted on matched FNAC, CNB, and surgical resection tissue samples obtained from breast cancer patients. The protein identification, including currently established or promising therapeutic targets, was compared among the three different sample types. Gene Ontology (GO) enrichment analysis was also performed on all matched samples.</p><p><strong>Results: </strong>Compared to tissue samples, FNAC testing revealed a comparable number of proteins (7,179 in FNAC; 7,196 in CNB; and 7,190 in resection samples). Around 85% of proteins were mutually identified in all sample types. FNAC, along with CNB, showed a positive correlation between the number of enrolled tumor cells and identified proteins. In the GO analysis, the FNAC samples demonstrated a higher number of genes for each pathway and GO terms than tissue samples. CCND1, CDK6, HER2, and IGF1R were found in higher quantities in the FNAC compared to tissue samples, while TUBB2A was only detected in the former.</p><p><strong>Conclusion: </strong>FNAC is suitable for high-throughput proteomic analysis, in addition to an emerging source that could be used to identify and quantify novel cancer biomarkers.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"359-369"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180365","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
Origin of Residual Tumor Masses in BRCA1/2-Driven Ovarian Carcinomas Treated by Neoadjuvant Chemotherapy: Selection of Preexisting BRCA1/2-Proficient Tumor Cells but Not the Gain of Second ORF-Restoring Mutation. 通过新辅助化疗治疗的 BRCA1/2 驱动的卵巢癌中残留肿瘤块的起源:选择已有的 BRCA1/2 基因纯合的肿瘤细胞,而非获得第二个 ORF 恢复突变。
IF 5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-08-14 DOI: 10.1159/000533591
Anna Sokolenko, Elena Preobrazhenskaya, Claudia Marchetti, Alessia Piermattei, Fedor Zagrebin, Ekatherina Kuligina, Tatiana Gorodnova, Matteo Pavone, Alexandr Ivantsov, Ilya Bizin, Giovanni Scambia, Igor Berlev, Anna Fagotti, Evgeny Imyanitov
{"title":"Origin of Residual Tumor Masses in BRCA1/2-Driven Ovarian Carcinomas Treated by Neoadjuvant Chemotherapy: Selection of Preexisting BRCA1/2-Proficient Tumor Cells but Not the Gain of Second ORF-Restoring Mutation.","authors":"Anna Sokolenko, Elena Preobrazhenskaya, Claudia Marchetti, Alessia Piermattei, Fedor Zagrebin, Ekatherina Kuligina, Tatiana Gorodnova, Matteo Pavone, Alexandr Ivantsov, Ilya Bizin, Giovanni Scambia, Igor Berlev, Anna Fagotti, Evgeny Imyanitov","doi":"10.1159/000533591","DOIUrl":"10.1159/000533591","url":null,"abstract":"<p><strong>Introduction: </strong>Tubo-ovarian carcinomas (OCs) are highly sensitive to platinum-based neoadjuvant chemotherapy (NACT) but almost never demonstrate complete pathologic response.</p><p><strong>Methods: </strong>We analyzed paired primary and residual tumor tissues from 30 patients with hereditary BRCA1/2-driven OCs (BRCA1: 17; BRCA2: 13), who were treated by carboplatin/paclitaxel NACT (median number of cycles: 3, range: 3-6). BRCA1/2 and TP53 genes were analyzed by the next-generation sequencing. The ratio between TP53 mutation-specific versus wild-type reads was considered to monitor the proportion of tumor and non-tumor cells in the tissue sample, and the ratio between BRCA1/2-mutated and wild-type reads was used to estimate the presence of cells with the loss or retention of heterozygosity (LOH or ROH, respectively).</p><p><strong>Results: </strong>All 30 OCs had BRCA1/2 LOH in primary tumor and carried somatic TP53 mutation. Twenty-eight OCs had sufficient tumor cell cellularity in the post-NACT tissue to evaluate the ratio between mutated and wild-type BRCA1/2 alleles. Five (18%) out of 28 informative tumor pairs showed transition from LOH to ROH during NACT presumably affecting all or the vast majority of residual tumor cells. There were no signals of the emergence of a second open reading frame-restoring BRCA1/2 mutation.</p><p><strong>Conclusion: </strong>Chemonaive BRCA1/2-driven carcinomas may contain a fraction of tumor cells with preserved BRCA1/2 heterozygosity. NACT can cause a selection of pre-existing BRCA1/2-proficient tumor cells, without gaining secondary reversal BRCA1/2 mutations.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"108-113"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10353147","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
Current State and Future Prospects of Diagnosis and Management of TP53-Mutated Myeloid Neoplasms. TP53突变型骨髓瘤诊断和治疗的现状与展望。
IF 5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-10-13 DOI: 10.1159/000534566
Sangeetha Venugopal, Sanam Loghavi
{"title":"Current State and Future Prospects of Diagnosis and Management of TP53-Mutated Myeloid Neoplasms.","authors":"Sangeetha Venugopal, Sanam Loghavi","doi":"10.1159/000534566","DOIUrl":"10.1159/000534566","url":null,"abstract":"<p><p>TP53-mutated myeloid neoplasms including acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS) are notoriously treatment resistant with uniformly poor outcomes. TP53 status is an important prognostic indicator and early knowledge of the TP53 mutation/allelic state may assist in appropriate management including clinical trial enrollment for eligible patients. Thus far, no therapy has shown to demonstrate durable response or incremental survival benefit in TP53-mutated AML or MDS. Therefore, there is an urgent need for innovative therapies to improve the outcomes in this notoriously recalcitrant genomic subset. In this review, we dissect the biology, classification, prognosis, current treatment landscape, and the early phase evaluation of investigational agents in TP53-mutated AML and MDS.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"45-54"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41237417","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
NPM1-Mutated Acute Myeloid Leukemia: Recent Developments and Open Questions. NPM1突变急性髓性白血病:最新进展与未决问题。
IF 5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-03-21 DOI: 10.1159/000530253
Sanjay S Patel
{"title":"NPM1-Mutated Acute Myeloid Leukemia: Recent Developments and Open Questions.","authors":"Sanjay S Patel","doi":"10.1159/000530253","DOIUrl":"10.1159/000530253","url":null,"abstract":"<p><p>Somatic mutations in the nucleophosmin (NPM1) gene occur in approximately 30% of de novo acute myeloid leukemias (AMLs) and are relatively enriched in normal karyotype AMLs. Earlier World Health Organization (WHO) classification schema recognized NPM1-mutated AMLs as a unique subtype of AML, while the latest WHO and International Consensus Classification (ICC) now consider NPM1 mutations as AML-defining, albeit at different blast count thresholds. NPM1 mutational load correlates closely with disease status, particularly in the post-therapy setting, and therefore high sensitivity-based methods for detection of the mutant allele have proven useful for minimal/measurable residual disease (MRD) monitoring. MRD status has been conventionally measured by either multiparameter flow cytometry (MFC) and/or molecular diagnostic techniques, although recent data suggest that MFC data may be potentially more challenging to interpret in this AML subtype. Of note, MRD status does not predict patient outcome in all cases, and therefore a deeper understanding of the biological significance of MRD may be required. Recent studies have confirmed that NPM1-mutated cells rely on overexpression of HOX/MEIS1, which is dependent on the presence of the aberrant cytoplasmic localization of mutant NPM1 protein (NPM1c); this biology may explain the promising response to novel agents, including menin inhibitors and second-generation XPO1 inhibitors. In this review, these and other recent developments around NPM1-mutated AML, in addition to open questions warranting further investigation, will be discussed.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"18-29"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10857804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9156719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IMP3 Immunohistochemical Expression Is Related with Progression and Metastases in Xenografted and Cutaneous Melanomas. IMP3免疫组织化学表达与异种移植和皮肤黑色素瘤的进展和转移有关。
IF 5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-10-05 DOI: 10.1159/000533916
Natividad Martin-Morales, Miguel Padial-Molina, Isabel Tovar, Virginea De Araujo Farias, Pedro Hernández-Cortés, Esperanza Ramirez-Moreno, Mercedes Caba-Molina, Justin Davis, Alejandro Carrero Castaño, Jose Mariano Ruiz de Almodovar, Pablo Galindo-Moreno, Javier Oliver-Pozo, Francisco Javier O'Valle Ravassa
{"title":"IMP3 Immunohistochemical Expression Is Related with Progression and Metastases in Xenografted and Cutaneous Melanomas.","authors":"Natividad Martin-Morales, Miguel Padial-Molina, Isabel Tovar, Virginea De Araujo Farias, Pedro Hernández-Cortés, Esperanza Ramirez-Moreno, Mercedes Caba-Molina, Justin Davis, Alejandro Carrero Castaño, Jose Mariano Ruiz de Almodovar, Pablo Galindo-Moreno, Javier Oliver-Pozo, Francisco Javier O'Valle Ravassa","doi":"10.1159/000533916","DOIUrl":"10.1159/000533916","url":null,"abstract":"<p><strong>Introduction: </strong>Insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3) over-expression is a predictor of tumor recurrence and metastases in some types of human melanoma. Our objective was to evaluate the immunohistochemical expression of IMP3 and other molecules related to tumor prognosis in melanoma-xeno-tumors undergoing treatment. We test the effect of radiotherapy (RT) and mesenchymal stromal cells (MSCs) treatment, analyzing the tumorigenic and metastatsizing capacity in a mice melanoma xenograft model.</p><p><strong>Materials and methods: </strong>We inoculated A375 and G361 human melanoma cell lines into NOD/SCID gamma mice (n = 64). We established a control group, a group treated with MSCs, a group treated with MSCs plus RT, and a group treated with RT. We assessed the immunohistochemical expression of IMP3, E-cadherin, N-cadherin, PARP1, HIF-1α, and the proliferation marker Ki-67. Additionally, we performed a retrospective study including 114 histological samples of patients diagnosed with malignant cutaneous superficial spreading melanoma (n = 104) and nodular melanoma (n = 10) with at least 5 years of follow-up.</p><p><strong>Results: </strong>Most morphological and immunohistochemical features show statistically significant differences between the 2 cell lines. The A375 cell line induced the formation of metastases, while the G361 cell line provoked tumor formation but not metastases. All three treatments reduced the cell proliferation evaluated by the Ki-67 nuclear antigen (p = 0.000, one-way ANOVA test) and reduced the number of metastases (p = 0.004, one-way ANOVA test). In addition, the tumor volumes reduced in comparison with the control groups, 31.74% for RT + MSCs in the A357 tumor cell line, and 89.84% RT + MSCs in the G361 tumor cell line. We also found that IMP3 expression is associated with greater tumor aggressiveness and was significantly correlated with cell proliferation (measured by the expression of Ki-67), the number of metastases, and reduced expression of adhesion molecules.</p><p><strong>Conclusions: </strong>The combined treatment of RT and MSCs on xenografted melanomas reduces tumor size, metastases frequency, and the epithelial to mesenchymal transition/PARP1 metastatic phenotype. This treatment also reduces the expression of molecules related to cellular proliferation (Ki-67), molecules that facilitate the metastatic process (E-cadherin), and molecules related with prognosis (IMP3).</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"132-143"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41129788","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
Gastric Polyps in Familial Adenomatous Polyposis Portuguese Patients: The First Western Cohort with Asian Features. 家族性腺瘤性息肉病葡萄牙患者的胃息肉:第一个具有亚洲特征的西方队列。
IF 5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-10-18 DOI: 10.1159/000534571
Diana Baptista, Marco Fernandes, Monica Garrido, Fabiana Sousa, Rui Morais, José Garcia-Pelaez, Roberto Silva, Dina Leitão, Manuela Baptista, José Barbosa, Fátima Carneiro, Irene Gullo
{"title":"Gastric Polyps in Familial Adenomatous Polyposis Portuguese Patients: The First Western Cohort with Asian Features.","authors":"Diana Baptista, Marco Fernandes, Monica Garrido, Fabiana Sousa, Rui Morais, José Garcia-Pelaez, Roberto Silva, Dina Leitão, Manuela Baptista, José Barbosa, Fátima Carneiro, Irene Gullo","doi":"10.1159/000534571","DOIUrl":"10.1159/000534571","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic atrophic gastritis may contribute to gastric polyps (GP) phenotype in familial adenomatous polyposis (FAP). Considering the high prevalence of Helicobacter pylori (HP) infection in Portugal, we aim to characterize GP in a series of Portuguese patients.</p><p><strong>Methods: </strong>In a retrospectively selected series of 53 FAP patients, clinical data and histopathological features of GP and background gastric mucosa were studied. SPSS (27.0) was used for statistical analysis.</p><p><strong>Results: </strong>Thirteen patients (24.5%) developed fundic gland polyps (FGP), seven (13.2%) gastric adenomas (GA), and ten (18.9%) both FGP and GA. Out of 100 GP, four were hyperplastic polyps, 58 FGP (24 with dysplasia), 35 intestinal-type GA (intGA), and three foveolar-type GA (fovGA). IntGA were larger (60% &gt;7 mm, p = 0.03), occurred predominantly in the distal stomach (66.7%, p = 0.024), in patients harboring gastric intestinal metaplasia (IM) (86.7%, p &lt; 0.001), and duodenal adenomas (86.7%, p &lt; 0.001).</p><p><strong>Conclusion: </strong>This is the first Western series showing high prevalence of intGA in FAP patients, comparable to Asian cohorts. HP infection and chronic atrophic gastritis/intestinal metaplasia are likely responsible for this difference, with risk of neoplastic transformation and management implications. Biopsy/excision of GP &gt;7 mm in the distal stomach and in patients harboring gastric intestinal metaplasia/duodenal adenomas should be considered.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"196-204"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49680833","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
Erratum. 勘误。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2024-07-31 DOI: 10.1159/000540330
{"title":"Erratum.","authors":"","doi":"10.1159/000540330","DOIUrl":"10.1159/000540330","url":null,"abstract":"","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"382"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860526","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
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