Experimental and molecular pathology最新文献

{"title":"Head and neck squamous cell carcinomas of unknown primary: Can ancillary studies help identify more primary tumor sites?","authors":"Troy Hutchens ,&nbsp;Wade Thorstad ,&nbsp;Xiaowei Wang ,&nbsp;Yuanxiang Li ,&nbsp;Eric J. Duncavage ,&nbsp;Lulu Sun ,&nbsp;Rebecca D. Chernock","doi":"10.1016/j.yexmp.2024.104915","DOIUrl":"10.1016/j.yexmp.2024.104915","url":null,"abstract":"<div><p>A subset of head and neck squamous cell carcinomas present solely as metastatic disease in the neck and are of unknown primary origin (SCCUP). Most primary tumors will ultimately be identified, usually in the oropharynx. In a minority of cases, the primary site remains elusive. Here, we examine the role of ancillary testing, including mutational signature analysis (MSA), to help identify likely primary sites in such cases. Twenty-two cases of SCCUP in the neck, collected over a 10-year period, were classified by morphology and viral status; including human papillomavirus (HPV) testing by p16 immunohistochemistry (IHC) and RT-qPCR, as well as Epstein-Barr virus (EBV) testing by EBER-ISH. CD5 and c-KIT (CD117) IHC was done to evaluate for possible thymic origin in all virus-negative cases. Whole exome sequencing, followed by MSA, was used to identify UV signature mutations indicative of cutaneous origin. HPV was identified in 12 of 22 tumors (54.5%), favoring an oropharyngeal origin, and closely associated with nonkeratinizing tumor morphology (Fisher's exact test; <em>p</em> = 0.0002). One tumor with indeterminant morphology had discordant HPV and p16 status (p16+/HPV-). All tumors were EBV-negative. Diffuse expression of CD5 and c-KIT was identified in 1 of 10 virus-negative SCCUPs (10%), suggesting a possible ectopic thymic origin rather than a metastasis. A UV mutational signature, indicating cutaneous origin, was identified in 1 of 10 (10%) virus-negative SCCUPs. A cutaneous auricular primary emerged 3 months after treatment in this patient. Primary tumors became clinically apparent in 2 others (1 hypopharynx, 1 hypopharynx/larynx). Thus, after follow-up, 6 tumors remained unclassifiable as to the possible site of origin (27%). Most SCCUPs of the neck in our series were HPV-associated and thus likely of oropharyngeal origin. UV signature mutation analysis and additional IHC for CD5 and c-KIT for possible thymic origin may aid in further classifying virus-negative unknown primaries. Close clinical inspection of hypopharyngeal mucosa may also be helpful, as a subset of primary tumors later emerged at this site.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"138 ","pages":"Article 104915"},"PeriodicalIF":2.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000340/pdfft?md5=f3c0e38b00d914f9416f2c7cc96f4521&pid=1-s2.0-S0014480024000340-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534043","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":"FANCD2 expression affects platinum response and further characteristics of high grade serous ovarian cancer in cells with different genetic backgrounds","authors":"Sarah J. Taylor ,&nbsp;Robert L. Hollis ,&nbsp;Charlie Gourley ,&nbsp;C. Simon Herrington ,&nbsp;Simon P. Langdon ,&nbsp;Mark J. Arends","doi":"10.1016/j.yexmp.2024.104916","DOIUrl":"https://doi.org/10.1016/j.yexmp.2024.104916","url":null,"abstract":"<div><p>High-grade serous ovarian cancer (HGSOC) is the most prevalent subtype of ovarian cancer and demonstrates 5-year survival of just 40%. One of the major causes of mortality is the development of tumour resistance to platinum-based chemotherapy, which can be modulated by dysregulation of DNA damage repair pathways. We therefore investigated the contribution of the DNA interstrand crosslink repair protein FANCD2 to chemosensitivity in HGSOC. Increased FANCD2 protein expression was observed in some cell line models of platinum resistant HGSOC compared with paired platinum sensitive models. Knockdown of FANCD2 in some cell lines, including the platinum resistant PEO4, led to increased carboplatin sensitivity. Investigation into mechanisms of FANCD2 regulation showed that increased FANCD2 expression in platinum resistant cells coincides with increased expression of mTOR. Treatment with mTOR inhibitors resulted in FANCD2 depletion, suggesting that mTOR can mediate platinum sensitivity via regulation of FANCD2. Tumours from a cohort of HGSOC patients showed varied nuclear and cytoplasmic FANCD2 expression, however this was not significantly associated with clinical characteristics. Knockout of FANCD2 was associated with increased cell migration, which may represent a non-canonical function of cytoplasmic FANCD2. We conclude that upregulation of FANCD2, possibly mediated by mTOR, is a potential mechanism of chemoresistance in HGSOC and modulation of FANCD2 expression can influence platinum sensitivity and other tumour cell characteristics.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"138 ","pages":"Article 104916"},"PeriodicalIF":2.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000352/pdfft?md5=08e7cce11ebe803a4d9ed746c4875b2b&pid=1-s2.0-S0014480024000352-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141485703","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":"Epithelial-mesenchymal transition associated markers in sarcomatoid transformation of clear cell renal cell carcinoma","authors":"Tanja Čugura,&nbsp;Emanuela Boštjančič,&nbsp;Sara Uhan,&nbsp;Nina Hauptman,&nbsp;Jera Jeruc","doi":"10.1016/j.yexmp.2024.104909","DOIUrl":"10.1016/j.yexmp.2024.104909","url":null,"abstract":"<div><p>Epithelial-mesenchymal transition (EMT) plays a pivotal role in the development and progression of many cancers. Partial EMT (pEMT) could represent a critical step in tumor migration and dissemination. Sarcomatoid renal cell carcinoma (sRCC) is an aggressive form of renal cell carcinoma (RCC) composed of a carcinomatous (sRCC-Ca) and sarcomatous (sRCC-Sa) component. The role of (p)EMT in the progression of RCC to sRCC remains unclear. The aim of this study was to investigate the involvement of (p)EMT in RCC and sRCC. Tissue samples from 10 patients with clear cell RCC (ccRCC) and 10 patients with sRCC were selected. The expression of main EMT markers (<em>miR-200</em> family, <em>miR-205</em>, <em>SNAI1/2, TWIST1/2, ZEB1/2</em>, <em>CDH1/2, VIM</em>) was analyzed by qPCR in ccRCC, sRCC-Ca, and sRCC-Sa and compared to non-neoplastic tissue and between both groups. Expression of E-cadherin, N-cadherin, vimentin and ZEB2 was analyzed using immunohistochemistry. <em>miR-200c</em> was downregulated in sRCC-Ca compared to ccRCC, while <em>miR-200a</em> was downregulated in sRCC-Sa compared to ccRCC. <em>CDH1</em> was downregulated in sRCC-Sa when compared to any other group. <em>ZEB2</em> was downregulated in ccRCC and sRCC compared to corresponding non-neoplastic kidney. A positive correlation was observed between <em>CDH1</em> expression and <em>miR-200a/b/c</em>. Our results suggest that full EMT is not present in sRCC. Instead, discreet molecular differences exist between ccRCC, sRCC-Ca, and sRCC-Sa, possibly representing distinct intermediary states undergoing pEMT.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"138 ","pages":"Article 104909"},"PeriodicalIF":3.6,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000285/pdfft?md5=7eb7984eba7d085c7bc82bc0b9fa6710&pid=1-s2.0-S0014480024000285-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320791","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":"Proteomic analysis of the effects of Dictyophora polysaccharide on arsenic-induced hepatotoxicity in rats","authors":"Xi Yan ,&nbsp;Xiaolu Chen ,&nbsp;Xinglai Zhang ,&nbsp;Ayesha Qureshi ,&nbsp;Yi Wang ,&nbsp;Xiaoxiao Tang ,&nbsp;Ting Hu ,&nbsp;Hongbin Zhuang ,&nbsp;Xiaoqian Ran ,&nbsp;Guanwei Ma ,&nbsp;Peng Luo ,&nbsp;Liming Shen","doi":"10.1016/j.yexmp.2024.104910","DOIUrl":"10.1016/j.yexmp.2024.104910","url":null,"abstract":"<div><p>Arsenic (As) is a highly toxic environmental toxicant and a known human carcinogen. Long-term exposure to As can cause liver injury. Dictyophora polysaccharide (DIP) is a biologically active natural compound found in the Dictyophora with excellent antioxidation, anti-inflammation, and immune protection properties. In this study, the Sprague-Dawley (SD) rat model of As toxicity was established using a feeding method, followed by DIP treatment in rats with As-induced liver injury. The molecular mechanisms of As toxicity to the rat liver and the protective effect of DIP were investigated by proteomic studies. The results showed that 172, 328 and 191 differentially expressed proteins (DEPs) were identified between the As-exposed rats versus control rats (As/Ctrl), DIP treated rats versus As-exposed rats (DIP+As/As), and DIP treated rats versus control rats (DIP+As /Ctrl), respectively. Among them, the expression of 90 DEPs in the As/Ctrl groups was reversed by DIP treatment. As exposure caused dysregulation of metabolic pathways, mitochondria, oxidative stress, and apoptosis-related proteins in the rat liver. However, DIP treatment changed or restored the levels of these proteins, which attenuated the damage to the livers of rats caused by As exposure. The results provide new insights into the mechanisms of liver injury induced by As exposure and the treatment of DIP in As poisoning.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"138 ","pages":"Article 104910"},"PeriodicalIF":3.6,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000297/pdfft?md5=96d76c89791a572195406a219a2cdc38&pid=1-s2.0-S0014480024000297-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320792","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":"Aberrant cell adhesiveness due to DNA hypermethylation of KLF11 in papillary urothelial carcinomas","authors":"Koji Tsumura ,&nbsp;Mao Fujimoto ,&nbsp;Ying Tian ,&nbsp;Toru Kawahara ,&nbsp;Hiroyuki Fujimoto ,&nbsp;Akiko Miyagi Maeshima ,&nbsp;Tohru Nakagawa ,&nbsp;Haruki Kume ,&nbsp;Teruhiko Yoshida ,&nbsp;Yae Kanai ,&nbsp;Eri Arai","doi":"10.1016/j.yexmp.2024.104908","DOIUrl":"10.1016/j.yexmp.2024.104908","url":null,"abstract":"<div><h3>Purpose</h3><p>The aim of this study was to clarify DNA methylation profiles determining the clinicopathological diversity of urothelial carcinomas.</p></div><div><h3>Methods</h3><p>Genome-wide DNA methylation analysis was performed using the Infinium HumanMethylation450 BeadChip in 46 paired samples of non-cancerous urothelium (N) and corresponding cancerous tissue (T), and 26 samples of normal control urothelium obtained from patients without urothelial carcinomas (C). For genes of interest, correlation between DNA methylation and mRNA expression was examined using the Cancer Genome Atlas database. In addition, the role of a selected target for cancer-relevant endpoints was further examined in urothelial carcinoma cell lines.</p></div><div><h3>Results</h3><p>The genes showing significant differences in DNA methylation levels between papillary carcinomas and more aggressive non-papillary (nodular) carcinomas were accumulated in signaling pathways participating in cell adhesion and cytoskeletal remodeling. Five hundred ninety-six methylation sites showed differences in DNA methylation levels between papillary and nodular carcinomas. Of those sites, that were located in CpG-islands around transcription start site, 5′-untranslated region or 1st exon, 16 genes exhibited inverse correlations between DNA methylation and mRNA expression levels. Among the latter, only the <em>KLF11</em> gene showed papillary T sample-specific DNA hypermethylation in comparison to C and N samples. The DNA methylation levels of <em>KLF11</em> were not significantly different between T samples and N samples or T samples and C samples for patients with papillo-nodular or nodular carcinomas. Knockdown experiments using the urothelial carcinoma cell lines HT1376 and 5637, which are considered models for papillary carcinoma, revealed that <em>KLF11</em> participates in altering the adhesiveness of cells to laminin-coated dishes, although cell growth was not affected.</p></div><div><h3>Conclusion</h3><p>These data indicate that DNA hypermethylation of <em>KLF11</em> may participate in the generation of papillary urothelial carcinomas through induction of aberrant cancer cell adhesion to the basement membrane.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"137 ","pages":"Article 104908"},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000273/pdfft?md5=f411ff946cdcef9045a6d24112b49eb9&pid=1-s2.0-S0014480024000273-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199186","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":"Overexpression of TSPAN8 in consensus molecular subtype 3 colorectal cancer","authors":"Thanawat Suwatthanarak ,&nbsp;Pariyada Tanjak ,&nbsp;Amphun Chaiboonchoe ,&nbsp;Onchira Acharayothin ,&nbsp;Kullanist Thanormjit ,&nbsp;Jantappapa Chanthercrob ,&nbsp;Tharathorn Suwatthanarak ,&nbsp;Apichaya Niyomchan ,&nbsp;Masayoshi Tanaka ,&nbsp;Mina Okochi ,&nbsp;Ananya Pongpaibul ,&nbsp;Wipapat Vicki Chalermwai ,&nbsp;Atthaphorn Trakarnsanga ,&nbsp;Asada Methasate ,&nbsp;Manop Pithukpakorn ,&nbsp;Vitoon Chinswangwatanakul","doi":"10.1016/j.yexmp.2024.104911","DOIUrl":"https://doi.org/10.1016/j.yexmp.2024.104911","url":null,"abstract":"<div><h3>Background</h3><p>Recently, consensus molecular subtypes (CMSs) have been proposed as a robust transcriptome-based classification system for colorectal cancer (CRC). Tetraspanins (TSPANs) are transmembrane proteins. They have been associated with the development of numerous malignancies, including CRC, through their role as “master organizers” for multi-molecular membrane complexes. No previous study has investigated the correlation between TSPANs and CMS classification. Herein, we investigated the expression of <em>TSPANs</em> in patient-derived primary CRC tissues and their CMS classifications.</p></div><div><h3>Methods</h3><p>RNA samples were derived from primary CRC tissues (<em>n</em> = 100 patients diagnosed with colorectal adenocarcinoma) and subjected to RNA sequencing for transcriptome-based CMS classification and <em>TSPAN</em>-relevant analyses. Immunohistochemistry (IHC) and immunofluorescence (IF) stains were conducted to observe the protein expression level. To evaluate the relative biological pathways, gene-set enrichment analysis was performed.</p></div><div><h3>Results</h3><p>Of the highly expressed <em>TSPAN</em> genes in CRC tissues (<em>TSPAN8</em>, <em>TSPAN29</em>, and <em>TSPAN30</em>), <em>TSPAN8</em> was notably overexpressed in CMS3-classified primary tissues. The overexpression of TSPAN8 protein in CMS3 CRC was also observed by IHC and IF staining. As a result of gene-set enrichment analysis, TSPAN8 may potentially play a role in organizing signaling complexes for kinase-based metabolic deregulation in CMS3 CRC.</p></div><div><h3>Conclusions</h3><p>The present study reports the overexpression of TSPAN8 in CMS3 CRC. This study proposes TSPAN8 as a subtype-specific biomarker for CMS3 CRC. This finding provides a foundation for future CMS-based studies of CRC, a complex disease and the second leading cause of cancer mortality worldwide.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"137 ","pages":"Article 104911"},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000303/pdfft?md5=15c2d35791f0b3b0f09481775a059ff3&pid=1-s2.0-S0014480024000303-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302820","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":"Congenital heart diseases (CHDs) and forensic investigations: Searching for the cause of death","authors":"Francesco Sessa ,&nbsp;Mario Chisari ,&nbsp;Monica Salerno ,&nbsp;Massimiliano Esposito ,&nbsp;Pietro Zuccarello ,&nbsp;Emanuele Capasso ,&nbsp;Edmondo Scoto ,&nbsp;Giuseppe Cocimano","doi":"10.1016/j.yexmp.2024.104907","DOIUrl":"10.1016/j.yexmp.2024.104907","url":null,"abstract":"<div><p>Congenital Heart Diseases (CHDs) are a group of structural abnormalities or defects of the heart that are present at birth. CHDs could be connected to sudden death (SD), defined by the WHO (World Health Organization) as “death occurring within 24 h after the onset of the symptoms” in an apparently “healthy” subject. These conditions can range from relatively mild defects to severe, life-threatening anomalies. The prevalence of CHDs varies across populations, but they affect millions of individuals worldwide. This article aims to discuss the post-mortem investigation of death related to CHDs, exploring the forensic approach, current methodologies, challenges, and potential advancements in this challenging field. A further goal of this article is to provide a guide for understanding these complex diseases, highlighting the pivotal role of autopsy, histopathology, and genetic investigations in defining the cause of death, and providing evidence about the translational use of autopsy reports. Forensic investigations play a crucial role in understanding the complexities of CHDs and determining the cause of death accurately. Through collaboration between medical professionals and forensic experts, meticulous examinations, and analysis of evidence, valuable insights can be gained. These insights not only provide closure to the families affected but also contribute to the prevention of future tragedies.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"137 ","pages":"Article 104907"},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000261/pdfft?md5=9b4b605caf3f9656c0222275136bb14d&pid=1-s2.0-S0014480024000261-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183892","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":"Accurate detection of copy number aberrations in FFPE samples using the mFAST-SeqS approach","authors":"Aude Jary ,&nbsp;Yongsoo Kim ,&nbsp;Kirsten Rozemeijer ,&nbsp;Paul P. Eijk ,&nbsp;Ramon P. van der Zee ,&nbsp;Maaike C.G. Bleeker ,&nbsp;Saskia M. Wilting ,&nbsp;Renske D.M. Steenbergen","doi":"10.1016/j.yexmp.2024.104906","DOIUrl":"10.1016/j.yexmp.2024.104906","url":null,"abstract":"<div><h3>Background</h3><p>Shallow whole genome sequencing (Shallow-seq) is used to determine the copy number aberrations (CNA) in tissue samples and circulating tumor DNA. However, costs of NGS and challenges of small biopsies ask for an alternative to the untargeted NGS approaches. The mFAST-SeqS approach, relying on LINE-1 repeat amplification, showed a good correlation with Shallow-seq to detect CNA in blood samples. In the present study, we evaluated whether mFAST-SeqS is suitable to assess CNA in small formalin-fixed paraffin-embedded (FFPE) tissue specimens, using vulva and anal HPV-related lesions.</p></div><div><h3>Methods</h3><p>Seventy-two FFPE samples, including 36 control samples (19 vulva;17 anal) for threshold setting and 36 samples (24 vulva; 12 anal) for clinical evaluation, were analyzed by mFAST-SeqS. CNA in vulva and anal lesions were determined by calculating genome-wide and chromosome arm-specific z-scores in comparison with the respective control samples. Sixteen samples were also analyzed with the conventional Shallow-seq approach.</p></div><div><h3>Results</h3><p>Genome-wide z-scores increased with the severity of disease, with highest values being found in cancers. In vulva samples median and inter quartile ranges [IQR] were 1[0–2] in normal tissues (<em>n</em> = 4), 3[1–7] in premalignant lesions (<em>n</em> = 9) and 21[13–48] in cancers (<em>n</em> = 10). In anal samples, median [IQR] were 0[0–1] in normal tissues (<em>n</em> = 4), 14[6–38] in premalignant lesions (n = 4) and 18[9–31] in cancers (n = 4). At threshold 4, all controls were CNA negative, while 8/13 premalignant lesions and 12/14 cancers were CNA positive. CNA captured by mFAST-SeqS were mostly also found by Shallow-seq.</p></div><div><h3>Conclusion</h3><p>mFAST-SeqS is easy to perform, requires less DNA and less sequencing reads reducing costs, thereby providing a good alternative for Shallow-seq to determine CNA in small FFPE samples.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"137 ","pages":"Article 104906"},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S001448002400025X/pdfft?md5=d05099e109fc94865c7001cbe5c5f572&pid=1-s2.0-S001448002400025X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183954","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":"Selenoprotein T, a potential treatment of attention-deficit/hyperactivity disorder and comorbid pain in neonatal 6-OHDA lesioned mice","authors":"Wahiba Sif-eddine ,&nbsp;Saadia Ba-M'hamed ,&nbsp;Benjamin Lefranc ,&nbsp;Jérôme Leprince ,&nbsp;Loubna Boukhzar ,&nbsp;Youssef Anouar ,&nbsp;Mohamed Bennis","doi":"10.1016/j.yexmp.2024.104905","DOIUrl":"https://doi.org/10.1016/j.yexmp.2024.104905","url":null,"abstract":"<div><p>pathological pain and Attention-deficit/hyperactivity disorder (ADHD) are two complex multifactorial syndromes. The comorbidity of ADHD and altered pain perception is well documented in children, adolescents, and adults. According to pathophysiological investigations, the dopaminergic system's dysfunction provides a common basis for ADHD and comorbid pain. Growing evidence suggests that oxidative stress may be crucial in both pathologies. Recent studies revealed that a small peptide encompassing the redox-active site of selenoprotein T (PSELT), protects dopaminergic neurons and fibers as well as lesioned nerves in animal models. The current study aims to examine the effects of PSELT treatment on ADHD-like symptoms and pain sensitivity, as well as the role of catecholaminergic systems in these effects. Our results demonstrated that intranasal administration of PSELT reduced the hyperactivity in the open field, decreased the impulsivity displayed by 6-OHDA-lesioned male mice in the 5-choice serial reaction time task test and improved attentional performance. In addition, PSELT treatment significantly increased the nociception threshold in both normal and inflammatory conditions. Furthermore, anti-hyperalgesic activity was antagonized with sulpiride pre-treatment, but not by phentolamine, or propranolol pre-treatments. The present study suggests that PSELT reduces the severity of ADHD symptoms in mice and possesses potent antinociceptive effects which could be related to the involvement of D2/D3 dopaminergic receptors.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"137 ","pages":"Article 104905"},"PeriodicalIF":3.6,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000248/pdfft?md5=2dba21dc712085718e4ed7cecfa848fb&pid=1-s2.0-S0014480024000248-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097702","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":"Advancements in nanomedicine: Precision delivery strategies for male pelvic malignancies – Spotlight on prostate and colorectal cancer","authors":"Guodong Yang ,&nbsp;Yu Cao ,&nbsp;Xinyi Yang ,&nbsp;Te Cui ,&nbsp;Nicole Zian Vi Tan ,&nbsp;Yuen Kai Lim ,&nbsp;Yu Fu ,&nbsp;Xinren Cao ,&nbsp;Aanchal Bhandari ,&nbsp;Mikhail Enikeev ,&nbsp;Sergey Efetov ,&nbsp;Vladimir Balaban ,&nbsp;Mingze He","doi":"10.1016/j.yexmp.2024.104904","DOIUrl":"10.1016/j.yexmp.2024.104904","url":null,"abstract":"<div><h3>Background</h3><p>Pelvic malignancies consistently pose significant global health challenges, adversely affecting the well-being of the male population. It is anticipated that clinicians will continue to confront these cancers in their practice. Nanomedicine offers promising strategies that revolutionize the treatment of male pelvic malignancies by providing precise delivery methods that aim to improve the efficacy of therapeutic outcomes while minimizing side effects. Nanoparticles are designed to encapsulate therapeutic agents and selectively target cancer cells. They can also be loaded with theragnostic agents, enabling multifunctional capabilities.</p></div><div><h3>Objective</h3><p>This review aims to summarize the latest nanomedicine research into clinical applications, focusing on nanotechnology-based treatment strategies for male pelvic malignancies, encompassing chemotherapy, radiotherapy, immunotherapy, and other cutting-edge therapies. The review is structured to assist physicians, particularly those with limited knowledge of biochemistry and bioengineering, in comprehending the functionalities and applications of nanomaterials.</p></div><div><h3>Methods</h3><p>Multiple databases, including PubMed, the National Library of Medicine, and Embase, were utilized to locate and review recently published articles on advancements in nano-drug delivery for prostate and colorectal cancers.</p></div><div><h3>Conclusion</h3><p>Nanomedicine possesses considerable potential in improving therapeutic outcomes and reducing adverse effects for male pelvic malignancies. Through precision delivery methods, this emerging field presents innovative treatment modalities to address these challenging diseases. Nevertheless, the majority of current studies are in the preclinical phase, with a lack of sufficient evidence to fully understand the precise mechanisms of action, absence of comprehensive pharmacotoxicity profiles, and uncertainty surrounding long-term consequences.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"137 ","pages":"Article 104904"},"PeriodicalIF":3.6,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000236/pdfft?md5=e21c92ac1952b1a4fb548238f34bc6bd&pid=1-s2.0-S0014480024000236-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093117","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}