Experimental and molecular pathology最新文献

{"title":"Circulating perturbation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is associated to cardiac remodeling and NLRP3 inflammasome in cardiovascular patients with insulin resistance risk","authors":"Elena Vianello ,&nbsp;Federico Ambrogi ,&nbsp;Marta Kalousová ,&nbsp;Julietta Badalyan ,&nbsp;Elena Dozio ,&nbsp;Lorenza Tacchini ,&nbsp;Gerd Schmitz ,&nbsp;Tomáš Zima ,&nbsp;Gregory J. Tsongalis ,&nbsp;Massimiliano M. Corsi-Romanelli","doi":"10.1016/j.yexmp.2024.104895","DOIUrl":"https://doi.org/10.1016/j.yexmp.2024.104895","url":null,"abstract":"<div><p>Lipidome perturbation occurring during meta-inflammation is associated to left ventricle (LV) remodeling though the activation of the NLRP3 inflammasome, a key regulator of chronic inflammation in obesity-related disorders. Little is known about phosphatidylcholine (PC) and phosphatidylethanolamine (PE) as DAMP-induced NLRP3 inflammasome. Our study is aimed to evaluate if a systemic reduction of PC/PE molar ratio can affect NLRP3 plasma levels in cardiovascular disease (CVD) patients with insulin resistance (IR) risk.</p><p>Forty patients from IRCCS Policlinico San Donato were enrolled, and their blood samples were drawn before heart surgery. LV geometry measurements were evaluated by echocardiography and clinical data associated to IR risk were collected. PC and PE were quantified by ESI-MS/MS. Circulating NLRP3 was quantified by an ELISA assay.</p><p>Our results have shown that CVD patients with IR risk presented systemic lipid impairment of PC and PE species and their ratio in plasma was inversely associated to NLRP3 levels. Interestingly, CVD patients with IR risk presented LV changes directly associated to increased levels of NLRP3 and a decrease in PC/PE ratio in plasma, highlighting the systemic effect of meta-inflammation in cardiac response. In summary, PC and PE can be considered bioactive mediators associated to both the NLRP3 and LV changes in CVD patients with IR risk.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"137 ","pages":"Article 104895"},"PeriodicalIF":3.6,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000145/pdfft?md5=b8fcafb846b5887387b776d9ad27b626&pid=1-s2.0-S0014480024000145-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825770","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}

{"title":"Effects of toll-like receptor agonists and SARS-CoV-2 antigens on interferon (IFN) expression by peripheral blood CD3+ T cells from COVID-19 patients","authors":"Samaneh Abdolmohammadi-Vahid ,&nbsp;Behzad Baradaran ,&nbsp;Armin Sadeghi ,&nbsp;Gilina Bezemer ,&nbsp;Fatemeh Kiaee ,&nbsp;Ian M. Adcock ,&nbsp;Gert Folkerts ,&nbsp;Johan Garssen ,&nbsp;Esmaeil Mortaz","doi":"10.1016/j.yexmp.2024.104897","DOIUrl":"https://doi.org/10.1016/j.yexmp.2024.104897","url":null,"abstract":"<div><h3>Background</h3><p>Signaling by toll-like receptors (TLRs) initiates important immune responses against viral infection. The role of TLRs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well elucidated. Thus, we investigated the interaction of TLRs agonists and SARS-COV-2 antigens with immune cells in vitro.</p></div><div><h3>Material &amp; methods</h3><p>30 coronavirus disease 2019 (COVID-19) patients (15 severe and 15 moderate) and 10 age and sex-matched healthy control (HC) were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and activated with TLR3, 7, 8, and 9 agonists, the spike protein (SP) of SARS-CoV-2, and the receptor binding domain (RBD) of SP. Frequencies of CD3⁺IFN-β⁺ T cells, and CD3⁺IFN-γ⁺ T cells were evaluated by flow cytometry. Interferon (IFN)-β gene expression was assessed by qRT-PCR.</p></div><div><h3>Results</h3><p>The frequency of CD3⁺IFN-β⁺ T cells was higher in PBMCs from moderate (<em>p</em> &lt; 0.0001) and severe (<em>p</em> = 0.009) patients at baseline in comparison with HCs. The highest increase in the frequency of CD3⁺IFN-β⁺ T cells in cell from moderate patients was induced by TLR8 agonist and SP (<em>p</em> &lt; 0.0001 for both) when compared to HC, while, the highest increase of the frequency of CD3⁺IFN-β⁺ T cells in sample of severe patients was seen with TLR8 and TLR7 agonists (both <em>p</em> = 0.002). The frequency of CD3⁺IFN-γ⁺ T cells was significantly increased upon stimulation with TLR agonists in cell from patients with moderate and severe COVID-19, compared with HC (all <em>p</em> &lt; 0.01), except with TLR7 and TLR8 agonists. The TLR8 agonist did not significantly increase the frequency of CD3⁺IFN-γ⁺ T cells in PBMCs of severe patients, but did so in cells from patients with moderate disease (<em>p</em> = 0.01). Moreover, IFN-β gene expression was significantly upregulated in CD3⁺T cells from moderate (<em>p</em> &lt; 0.0001) and severe (<em>p</em> = 0.002) COVID-19 patients, compared to HC after stimulation with the TLR8 agonist, while, stimulation of T cells with SP, significantly up-regulated IFN-β mRNA expression in cells from patients with moderate (<em>p</em> = 0.0003), but not severe disease.</p></div><div><h3>Conclusion</h3><p>Stimulation of PBMCs from COVID-19 patients, especially patients with moderate disease, with TLR8 agonist and SP increased the frequency of IFN-β-producing T cells and IFN-β gene expression.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"137 ","pages":"Article 104897"},"PeriodicalIF":3.6,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000169/pdfft?md5=3fd93203ce33e5c1984c989354a244d5&pid=1-s2.0-S0014480024000169-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140816940","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}

{"title":"Decreased proteasome function increases oxidative stress in the early stage of pressure ulcer development","authors":"Eri Murata ,&nbsp;Takuma Yoshida ,&nbsp;Utano Tomaru ,&nbsp;Saaki Yamamoto ,&nbsp;Aya Fukui-Miyazaki ,&nbsp;Akihiro Ishizu ,&nbsp;Masanori Kasahara","doi":"10.1016/j.yexmp.2024.104891","DOIUrl":"10.1016/j.yexmp.2024.104891","url":null,"abstract":"<div><p>The aging process in the elderly results in heightened skin fragility associated with various disorders, including pressure ulcers (PUs). Despite the high incidence of PUs in the elderly population, there is a limited body of research specifically examining the impact of aging on the development of pressure ulcers. Therefore, investigating age-related physiological abnormalities is essential to elucidate the pathogenesis of PUs. Ischemia-reperfusion (I/R) injury and the subsequent oxidative stress caused by reactive oxygen species (ROS) play essential roles in the early stage of PUs. In this study, we used a mouse model of proteasomal dysfunction with an age-related phenotype to examine the role of proteasome activity in cutaneous I/R injury <em>in vivo</em>. Decreased proteasome function did not affect the expression of inflammatory cytokines and adhesion molecules in the I/R area in transgenic mice; however, proteasome inhibition increased oxidative stress that was not attenuated by activation of the oxidative stress response mediated by NF-E2-related factor 2 (Nrf2). In dermal fibroblasts (FCs) subjected to hypoxia-reoxygenation (H/R), proteasome inhibition induced oxidative stress and ROS production, and Nrf2 activation did not adequately upregulate antioxidant enzyme expression, possibly leading to antioxidant/oxidant imbalance. The free radical scavenger edaravone had protective effects against I/R injury <em>in vivo</em> and decreased oxidative stress in FCs treated with a proteasome inhibitor and subjected to H/R <em>in vitro</em>. The results suggest that the age-related decline in proteasome activity promotes cutaneous I/R injury-induced oxidative stress, and free radical scavengers may exert protective effects by preventing oxidative stress in the early stage of PUs.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"137 ","pages":"Article 104891"},"PeriodicalIF":3.6,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000108/pdfft?md5=f1f9ec6172e98a6e919439d4fa27ed6c&pid=1-s2.0-S0014480024000108-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093744","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}

{"title":"TBX15 and SDHB expression changes in colorectal cancer serve as potential prognostic biomarkers","authors":"Melika Golozar ,&nbsp;Ali Valipour Motlagh ,&nbsp;Mohammad Mahdevar ,&nbsp;Maryam Peymani ,&nbsp;Kolsoum InanlooRahatloo ,&nbsp;Kamran Ghaedi","doi":"10.1016/j.yexmp.2024.104890","DOIUrl":"10.1016/j.yexmp.2024.104890","url":null,"abstract":"<div><p>Alterations in the expression of certain genes could be associated with both patient mortality rates and drug resistance. This study aimed to identify genes in colorectal cancer (CRC) that potentially serve as hub genes influencing patient survival rates. RNA-Seq data were downloaded from the cancer genome atlas database, and differential expression analysis was performed between tumors and healthy controls. Through the utilization of univariate and multivariate Cox regression analyses, in combination with the MCODE clustering module, the genes whose expression changes were related to survival rate and the hub genes related to them were identified. The mortality risk model was computed using the hub genes. CRC samples and the RT-qPCR method were utilized to confirm the outcomes. PharmacoGx data were employed to link the expression of potential genes to medication resistance and sensitivity. The results revealed the discovery of seven hub genes, which emerged as independent prognostic markers. These included <em>HOXC6</em>, <em>HOXC13</em>, <em>HOXC8</em>, and <em>TBX15</em>, which were associated with poor prognosis and overexpression, as well as <em>SDHB</em>, <em>COX5A</em>, and <em>UQCRC1</em>, linked to favorable prognosis and downregulation. Applying the risk model developed with the mentioned genes revealed a markedly higher incidence of deceased patients in the high-risk group compared to the low-risk group. RT-qPCR results indicated a decrease in <em>SDHB</em> expression and an elevation in <em>TBX15</em> levels in cancer samples relative to adjacent healthy tissue. Also, PharmacoGx data indicated that the expression level of <em>SDHB</em> was correlated with drug sensitivity to Crizotinib and Dovitinib. Our findings highlight the potential association between alterations in the expression of genes such as <em>HOXC6</em>, <em>HOXC13</em>, <em>HOXC8</em>, <em>TBX15</em>, <em>SDHB</em>, <em>COX5A</em>, and <em>UQCRC1</em> and increased mortality rates in CRC patients. As revealed by the PPI network, these genes exhibited the most connections with other genes linked to survival.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"136 ","pages":"Article 104890"},"PeriodicalIF":3.6,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000091/pdfft?md5=81cba468dad9389365dfdf0369be2e8e&pid=1-s2.0-S0014480024000091-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912433","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}

{"title":"Molecular and cellular pruritus mechanisms in the host skin","authors":"Li Li ,&nbsp;Zhi-en Li ,&nbsp;Yun-li Mo ,&nbsp;Wan-yao Li ,&nbsp;Hui-jing Li ,&nbsp;Guang-hai Yan ,&nbsp;Xiang-zheng Qin ,&nbsp;Li-hua Piao","doi":"10.1016/j.yexmp.2024.104889","DOIUrl":"10.1016/j.yexmp.2024.104889","url":null,"abstract":"<div><p>Pruritus, also known as itching, is a complex sensation that involves the activation of specific physiological and cellular receptors. The skin is innervated with sensory nerves as well as some receptors for various sensations, and its immune system has prominent neurological connections. Sensory neurons have a considerable impact on the sensation of itching. However, immune cells also play a role in this process, as they release pruritogens. Disruption of the dermal barrier activates an immune response, initiating a series of chemical, physical, and cellular reactions. These reactions involve various cell types, including keratinocytes, as well as immune cells involved in innate and adaptive immunity. Collective activation of these immune responses confers protection against potential pathogens. Thus, understanding the molecular and cellular mechanisms that contribute to pruritus in host skin is crucial for the advancement of effective treatment approaches. This review provides a comprehensive analysis of the present knowledge concerning the molecular and cellular mechanisms underlying itching signaling in the skin. Additionally, this review explored the integration of these mechanisms with the broader context of itch mediators and the expression of their receptors in the skin.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"136 ","pages":"Article 104889"},"PeriodicalIF":3.6,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S001448002400008X/pdfft?md5=a2beb07942952267e359459ae10328ef&pid=1-s2.0-S001448002400008X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691587","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}

{"title":"Experimental models in Familial Mediterranean Fever (FMF): Insights into pathophysiology and therapeutic strategies","authors":"Nawal Mezher ,&nbsp;Ola Mroweh ,&nbsp;Louna Karam,&nbsp;José-Noel Ibrahim,&nbsp;Philippe Hussein Kobeissy","doi":"10.1016/j.yexmp.2024.104883","DOIUrl":"10.1016/j.yexmp.2024.104883","url":null,"abstract":"<div><p>Familial Mediterranean Fever (FMF) is a recurrent polyserositis characterized by self-limiting episodes or attacks of fever along with serosal inflammation. It mainly impacts people of the Mediterranean and Middle Eastern basin. FMF is a recessive autoinflammatory condition caused by mutation in the <em>MEFV</em> gene located on chromosome 16p13. <em>MEFV</em> mutations lead to the activation of the pyrin inflammasome resulting in an uncontrolled release of IL-1β. Various <em>in vitro</em>, <em>in vivo</em> and <em>ex vivo</em> experimental models have been developed to further comprehend the etiology and pathogenesis of FMF. These models have been proven to be clinically relevant to human FMF and can provide significant information about biological systems with respect to this condition. Additionally, these models have provided pertinent contributions to the development of potent therapeutic strategies against FMF. In this review, we describe the different experimental models utilized in FMF and we focus primarily on the most widely used models that have produced prominent insights into the pathophysiology of the disease.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"135 ","pages":"Article 104883"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000029/pdfft?md5=bb58ddaf7c248d2031ad07c65c126e39&pid=1-s2.0-S0014480024000029-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546020","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}

{"title":"CD10 expression as a potential predictor of pathological complete response in ER-negative and triple-negative breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy","authors":"George Dimitrov ,&nbsp;Sami Shousha ,&nbsp;Petranka Troianova","doi":"10.1016/j.yexmp.2024.104885","DOIUrl":"10.1016/j.yexmp.2024.104885","url":null,"abstract":"<div><h3>Background</h3><p>Neoadjuvant chemotherapy (NCT) can induce a pathological complete response (pCR) in breast cancer patients, leading to improved outcomes. However, predicting which patients will achieve pCR remains a challenge. CD10, a myoepithelial marker, has shown diagnostic and prognostic value in metastatic tumors. Its potential as a predictor of chemosensitivity to anthracycline-based NCT in breast cancer is unknown.</p></div><div><h3>Aim</h3><p>This retrospective study aimed to investigate the potential of CD10 cancer cell expression as a predictive marker of chemosensitivity in breast cancers treated with anthracycline-based neoadjuvant chemotherapy.</p></div><div><h3>Methods</h3><p>We analyzed 130 patients with invasive ductal carcinoma who received anthracycline-based NCT. CD10 expression was assessed by immunohistochemistry on pre-treatment biopsies. Statistical analysis evaluated the association between CD10 expression and pCR rates.</p></div><div><h3>Results</h3><p>Univariate analysis revealed that ER-positive and CD10-negative tumors had lower pCR rates [OR 7.4830 (95% CI 2.7762–20.1699); <em>p</em> = 0.0001]. Multivariate analysis confirmed ER status as a strong predictor of poor response [OR 0.085 (95% CI 0.024–0.30); <em>p</em> &lt; 0.001] and CD10 expression as a predictor of a favourable response [OR 0.11 (0.8–0.19); <em>p</em> = 0.049]. CD10 expression significantly predicted pCR in ER-negative cases [OR 0.1098 (0.0268–0.4503); <em>p</em> = 0.0022] and triple-negative breast cancer [OR 0.0966 (95% CI 0.0270–0.3462); <em>p</em> = 0.0003]. Concordance was observed between core biopsies and excised samples.</p></div><div><h3>Conclusion</h3><p>Positive CD10 cancer cell expression may predict increased response to anthracycline-based neoadjuvant chemotherapy in ER-negative and triple-negative breast cancer cases. Further research is needed to validate these findings in larger cohorts and determine the clinical utility of CD10 as a predictive marker.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"135 ","pages":"Article 104885"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000042/pdfft?md5=aefb1618026e0da730b2791cf9888988&pid=1-s2.0-S0014480024000042-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569804","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}

{"title":"Interleukin 6 polymorphisms are associated with cardiovascular risk factors in premature coronary artery disease patients and healthy controls of the GEA Mexican study","authors":"Rosalinda Posadas-Sánchez ,&nbsp;Ángel Rene López-Uribe ,&nbsp;José Manuel Fragoso ,&nbsp;Gilberto Vargas-Alarcón","doi":"10.1016/j.yexmp.2024.104886","DOIUrl":"10.1016/j.yexmp.2024.104886","url":null,"abstract":"<div><h3>Background and aims</h3><p>Interleukin-6 (IL-6) is an acute-phase protein that plays an important role in the inflammatory response, vascular inflammation, and atherosclerosis process. The study aimed to establish whether <em>IL-6</em> gene polymorphisms and IL-6 concentrations are associated with premature coronary artery disease (pCAD) and cardiovascular risk factors.</p></div><div><h3>Methods</h3><p>The IL-6 concentrations and the rs2069827, rs1800796, and rs1800795 IL-6 polymorphisms were determined in 1150 pCAD patients and 1083 healthy controls (coronary artery calcium equal to zero determined by tomography).</p></div><div><h3>Results</h3><p>The <em>IL-6</em> polymorphisms studied were not associated with pCAD, but they were associated with cardiovascular risk factors in patients and controls. In controls, under the dominant model, the rs1800795 <em>C</em> allele and the rs2069827 <em>T</em> allele were associated with a low risk of central obesity (OR = 0.401, <em>p</em> = 0.017 and OR = 0.577, <em>p</em> = 0.031, respectively), hypoalphalipoproteinemia (OR = 0.581, <em>p</em> = 0.027 and OR = 0.700, <em>p</em> = 0.014, respectively) and hypertriglyceridemia (OR = 0.575, <em>p</em> = 0.030 and OR = 0.728, <em>p</em> = 0.033, respectively). In pCAD, the rs1800795 <em>C</em> allele was associated with an increased risk of hypoalphalipoproteinemia (OR = 1.370, <em>p</em>_additive = 0.025) and increased C-reactive protein (CRP) concentrations (OR = 1.491, <em>p</em>_additive = 0.007). pCAD patients had significantly higher serum IL-6 concentrations compared to controls (<em>p</em> = 0.002). In the total population, individuals carrying the rs1800795 <em>GC + CC</em> genotypes had higher levels of IL-6 than carriers of the <em>GG</em> genotype (<em>p</em> = 0.025). In control individuals carrying the <em>C</em> allele (<em>CG + CC</em>), an inverse correlation was observed between IL-6 and HDL-cholesterol levels (<em>p</em> = 0.003).</p></div><div><h3>Conclusions</h3><p>In summary, the <em>IL-6</em> polymorphisms were not associated with pCAD, however, they were associated with cardiovascular risk factors in pCAD patients and healthy controls. Individuals carrying the rs1800795 <em>GC + CC</em> genotypes had higher levels of IL-6 than carriers of the <em>GG</em> genotype.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"136 ","pages":"Article 104886"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000054/pdfft?md5=cca370e10e0d5fbb3a699bf21646d904&pid=1-s2.0-S0014480024000054-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139641949","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}

{"title":"Environmental physical factors produce mitotic aberration and multicellularity in the ovarian cancer cell line SKOV3.","authors":"N Lujea, F Chiola, M De Leon Rodriguez, C Acosta, P Kunda","doi":"10.1016/j.yexmp.2024.104884","DOIUrl":"https://doi.org/10.1016/j.yexmp.2024.104884","url":null,"abstract":"<p><p>The spread of ovarian cancer (OC) to the coelomic cavity triggers the secretion and accumulation of ascitic fluid (AF). Although its biochemical composition has been well studied, less is known about the implications of physical factors such as the pH and the mechanical properties of the AF for the malignancy of tumor cells. In this work, we investigated the effect of pH and the mechanical properties of AF on cell proliferation and mitotic morphology. We employed biopsies from patients with OC and the SKOV3 cell line as an in vitro model of OC with HeLa cells as controls. Sections of each tumor were stained with HE, analyzed, and related to clinical data. AF from patients with OC exhibited an alkaline pH (ranging from 7.3 to 7.8). Compared to control conditions, the 3 AFs significantly enhanced the proliferation of SKOV3 and HeLa cells. These effects were more pronounced at a more alkaline pH. In addition, we found that AFs have different densities that correlated with a significant increase in multinucleated tumor cells and severe morphological defects in cells undergoing mitosis. In agreement with these data, we found that higher concentrations of soft agar provoked significantly higher numbers of multinucleated and morphologically abnormal SKOV3 cells with no effect on HeLa cells. We conclude that an alkaline pH and greater rigidity could enhance the metastatic potential of OC cells. We propose that these two physical factors could be parameters of clinical importance as predictors of malignancy.</p>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":" ","pages":"104884"},"PeriodicalIF":3.6,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575028","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}

{"title":"An in-silico analysis reveals further evidence of an aggressive subset of lung carcinoids sharing molecular features of high-grade neuroendocrine neoplasms","authors":"Giuseppe Pelosi ,&nbsp;Valentina Melocchi ,&nbsp;Elisa Dama ,&nbsp;Paul Hofman ,&nbsp;Marco De Luca ,&nbsp;Adriana Albini ,&nbsp;Maria Gemelli ,&nbsp;Riccardo Ricotta ,&nbsp;Mauro Papotti ,&nbsp;Stefano La Rosa ,&nbsp;Silvia Uccella ,&nbsp;Sergio Harari ,&nbsp;Angelica Sonzogni ,&nbsp;Michael K. Asiedu ,&nbsp;Dennis A. Wigle ,&nbsp;Fabrizio Bianchi","doi":"10.1016/j.yexmp.2024.104882","DOIUrl":"10.1016/j.yexmp.2024.104882","url":null,"abstract":"<div><p>Little is known as to whether there may be any pathogenetic link between pulmonary carcinoids and neuroendocrine carcinomas (NECs). A gene signature we previously found to cluster pulmonary carcinoids, large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC), and which encompassed <em>MEN1, MYC, MYCL1, RICTOR, RB1, SDHA, SRC</em> and <em>TP53 mutations or</em> copy number variations (CNVs), was used to reclassify an independent cohort of 54 neuroendocrine neoplasms (NENs) [31 typical carcinoids (TC), 11 atypical carcinoids (AC) and 12 SCLC], by means of transcriptome and mutation data. Unsupervised clustering analysis identified two histology-independent clusters, namely CL1 and CL2, where 17/42 (40.5%) carcinoids and all the SCLC samples fell into the latter. CL2 carcinoids affected survival adversely, were enriched in T to G transversions or T &gt; C/C &gt; T transitions in the context of specific mutational signatures, presented with at least 1.5-fold change (FC) increase of gene mutations including <em>TSC2</em>, <em>SMARCA2</em>, <em>SMARCA4</em>, <em>ERBB4</em> and <em>PTPRZ1</em>, differed for gene expression and showed epigenetic changes in charge of <em>MYC</em> and <em>MTORC1</em> pathways, cellular senescence, inflammation, high-plasticity cell state and immune system exhaustion. Similar results were also found in two other independent validation sets comprising 101 lung NENs (24 carcinoids, 21 SCLC and 56 LCNEC) and 30 carcinoids, respectively. We herein confirmed an unexpected sharing of molecular traits along the spectrum of lung NENs, with a subset of genomically distinct aggressive carcinoids sharing molecular features of high-grade neuroendocrine neoplasms.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"135 ","pages":"Article 104882"},"PeriodicalIF":3.6,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000017/pdfft?md5=8e18b58028ce704033d84572f79c139a&pid=1-s2.0-S0014480024000017-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490897","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}