Non-coding RNAs (ncRNAs) have become important modulators of gene expression and biological processes, contributing significantly to the initiation and spread of cancer. This study focuses on the complex interactions between ncRNAs and two major signaling pathways—Wnt/β-catenin signaling and cyclin-dependent kinase (CDK)—linked to cancer. We provide an overview of current research on the modulation of these pathways in many cancer types by distinct classes of ncRNAs, such as miRNAs, lncRNAs, and circRNAs. The review focuses on the processes by which ncRNAs regulate cancer cell survival, proliferation, and metastasis. These mechanical processes include CDK activity, the activation of the Wnt/β-catenin cascade and cell cycle advancement. We also discuss the importance of ncRNAs in drug resistance and treatment outcomes, as well as prognosis markers (diagnostic) and therapeutic targets for cancer. Understanding these complex regulatory networks may help in a large way to improve cancer research and diagnosis - but also perhaps treat patients more effectively.
{"title":"Non-coding RNAs: Key regulators of CDK and Wnt/β-catenin signaling in cancer","authors":"Mohammad Arshad Javed Shaikh , M.Arockia Babu , Nehmat Ghaboura , Abdulmalik S.A. Altamimi , Pawan Sharma , Richa Rani , G.B. Rani , Sorabh Lakhanpal , Haider Ali , Ashok Kumar Balaraman , Sushama Rawat , Sami I. Alzarea , Imran Kazmi","doi":"10.1016/j.prp.2024.155659","DOIUrl":"10.1016/j.prp.2024.155659","url":null,"abstract":"<div><div>Non-coding RNAs (ncRNAs) have become important modulators of gene expression and biological processes, contributing significantly to the initiation and spread of cancer. This study focuses on the complex interactions between ncRNAs and two major signaling pathways—Wnt/β-catenin signaling and cyclin-dependent kinase (CDK)—linked to cancer. We provide an overview of current research on the modulation of these pathways in many cancer types by distinct classes of ncRNAs, such as miRNAs, lncRNAs, and circRNAs. The review focuses on the processes by which ncRNAs regulate cancer cell survival, proliferation, and metastasis. These mechanical processes include CDK activity, the activation of the Wnt/β-catenin cascade and cell cycle advancement. We also discuss the importance of ncRNAs in drug resistance and treatment outcomes, as well as prognosis markers (diagnostic) and therapeutic targets for cancer. Understanding these complex regulatory networks may help in a large way to improve cancer research and diagnosis - but also perhaps treat patients more effectively.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155659"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505689","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}
Pub Date : 2024-10-14DOI: 10.1016/j.prp.2024.155656
Sudipta Naskar , Ipseet Mishra , B.S. Srinath , Rekha V. Kumar , Drugadevi Veeraiyan , Pooja Melgiri , Hari P S , Manjunath Sastry , Venkatachala K. , Aruna Korlimarla
Introduction
MicroRNAs (MIRs) play a crucial role in colorectal cancer (CRC) development and metastasis by regulating immune responses. Tumour-infiltrating lymphocytes (TILs) are an important predictive factor in many cancers, but, their association with microRNAs have not been studied well in colorectal cancer. Three microRNAs (MIR34A, MIR31 & MIR21), the roles of which in tumorigenesis is well-studied and which also possess immunomodulatory effect, were identified by extensive literature search. Of these, MIR34A acts as a tumour suppressor, MIR21 is considered an onco-MIR, and MIR31 displays both tumour-suppressing and oncogenic properties, making it ambiguous. This study examines the relationship between these three micro-RNAs and TILs in CRC.
Materials & methods
Conducted over 18 months at a tertiary cancer care hospital in southern India, this unicentric observational study included 69 cases. These cases were analyzed for miR expression using q-RT-PCR, TILs density through hematoxylin & eosin(H&E) slide examination, and p53 and beta-catenin expression via immunohistochemistry (IHC). Correlations between non-parametric variables were assessed using Chi-square and Spearman correlation tests.
Results
The study found significantly higher MIR34A expression in patients aged 60 years and less (26/41, p=0.024) and a higher prevalence of MIR21 in male patients (23/35, p=0.012). TILs at the tumour advancing front were categorized as low (≤10 %) or high (≥15 %). Among the 36 cases with low TILs, high MIR34A and high MIR31 expressions were observed in 24 cases (p=0.016) and 23 cases (p=0.03), respectively. Conversely, 21 of 33 cases with high TILs had low expressions of both MIR34A and MIR31. High TILs were more common in early-stage CRC (TNM stages I-IIIA), with 20 out of 28 cases, compared to 28 of 41 cases in later stages (IIIB-IVC) exhibiting low TILs (p=0.003). Aberrant p53 expression correlated with lower MIR34A levels, consistent with TCGA data.
Conclusion
Lower MIR34A and MIR31 levels are associated with higher TILs density in CRC. Unlike other cancers where MIR34A has anti-tumour effects, there was no statistically significant correlation between its expression and the pT or TNM stages in this study. Increased TILs being a good prognostic indicator, this suggests MIR34A and MIR31 may help CRC cells evade immune surveillance. Aberrant p53 expression downregulates MIR34A, underscoring the therapeutic potential of miRs.
{"title":"Lower expressions of MIR34A and MIR31 in colo-rectal cancer are associated with an enriched immune microenvironment","authors":"Sudipta Naskar , Ipseet Mishra , B.S. Srinath , Rekha V. Kumar , Drugadevi Veeraiyan , Pooja Melgiri , Hari P S , Manjunath Sastry , Venkatachala K. , Aruna Korlimarla","doi":"10.1016/j.prp.2024.155656","DOIUrl":"10.1016/j.prp.2024.155656","url":null,"abstract":"<div><h3>Introduction</h3><div>MicroRNAs (MIRs) play a crucial role in colorectal cancer (CRC) development and metastasis by regulating immune responses. Tumour-infiltrating lymphocytes (TILs) are an important predictive factor in many cancers, but, their association with microRNAs have not been studied well in colorectal cancer. Three microRNAs (MIR34A, MIR31 & MIR21), the roles of which in tumorigenesis is well-studied and which also possess immunomodulatory effect, were identified by extensive literature search. Of these, MIR34A acts as a tumour suppressor, MIR21 is considered an onco-MIR, and MIR31 displays both tumour-suppressing and oncogenic properties, making it ambiguous. This study examines the relationship between these three micro-RNAs and TILs in CRC.</div></div><div><h3>Materials & methods</h3><div>Conducted over 18 months at a tertiary cancer care hospital in southern India, this unicentric observational study included 69 cases. These cases were analyzed for miR expression using q-RT-PCR, TILs density through hematoxylin & eosin(H&E) slide examination, and p53 and beta-catenin expression via immunohistochemistry (IHC). Correlations between non-parametric variables were assessed using Chi-square and Spearman correlation tests.</div></div><div><h3>Results</h3><div>The study found significantly higher MIR34A expression in patients aged 60 years and less (26/41, p=0.024) and a higher prevalence of MIR21 in male patients (23/35, p=0.012). TILs at the tumour advancing front were categorized as low (≤10 %) or high (≥15 %). Among the 36 cases with low TILs, high MIR34A and high MIR31 expressions were observed in 24 cases (p=0.016) and 23 cases (p=0.03), respectively. Conversely, 21 of 33 cases with high TILs had low expressions of both MIR34A and MIR31. High TILs were more common in early-stage CRC (TNM stages I-IIIA), with 20 out of 28 cases, compared to 28 of 41 cases in later stages (IIIB-IVC) exhibiting low TILs (p=0.003). Aberrant p53 expression correlated with lower MIR34A levels, consistent with TCGA data.</div></div><div><h3>Conclusion</h3><div>Lower MIR34A and MIR31 levels are associated with higher TILs density in CRC. Unlike other cancers where MIR34A has anti-tumour effects, there was no statistically significant correlation between its expression and the pT or TNM stages in this study. Increased TILs being a good prognostic indicator, this suggests MIR34A and MIR31 may help CRC cells evade immune surveillance. Aberrant p53 expression downregulates MIR34A, underscoring the therapeutic potential of miRs.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155656"},"PeriodicalIF":2.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505687","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}
Pub Date : 2024-10-11DOI: 10.1016/j.prp.2024.155654
Min Hee Yang , Seung Ho Baek , Young Yun Jung , Jae-Young Um , Kwang Seok Ahn
Micheliolide (MCL), a naturally occurring sesquiterpene lactone, has demonstrated significant anticancer properties through the induction of various programmed cell death mechanisms. This study aimed to explore MCL's effects on autophagy, paraptosis, and ferroptosis in pancreatic and colon cancer cells, along with its modulation of the MAPK signaling pathway. MCL was found to substantially suppress cell viability in these cancer cells, particularly in MIA PaCa-2 and HT-29 cell lines. The study identified that MCL induced autophagy by enhancing the levels of autophagy markers such as Atg7, p-Beclin-1, and Beclin-1, which was attenuated by the autophagy inhibitor 3-MA. Furthermore, MCL was found to facilitate paraptosis, indicated by decreased Alix and in-creased ATF4 and CHOP levels. It also promoted ferroptosis, as demonstrated by the reduced expression of SLC7A11, elevated TFRC levels, and increased intracellular iron. Additionally, MCL activated the MAPK signaling pathway, marked by the phosphorylation of JNK, p38, and ERK, linked with an increase in ROS production that is vital in regulating these cell death mechanisms. These findings propose that MCL is a versatile anticancer agent, capable of activating various cell death pathways by modulating MAPK signaling and ROS levels. These results emphasize the therapeutic promise of MCL in treating cancer, pointing to the necessity of further in vivo investigations to confirm these effects and determine its potential clinical uses.
{"title":"Activation of autophagy, paraptosis, and ferroptosis by micheliolide through modulation of the MAPK signaling pathway in pancreatic and colon tumor cells","authors":"Min Hee Yang , Seung Ho Baek , Young Yun Jung , Jae-Young Um , Kwang Seok Ahn","doi":"10.1016/j.prp.2024.155654","DOIUrl":"10.1016/j.prp.2024.155654","url":null,"abstract":"<div><div>Micheliolide (MCL), a naturally occurring sesquiterpene lactone, has demonstrated significant anticancer properties through the induction of various programmed cell death mechanisms. This study aimed to explore MCL's effects on autophagy, paraptosis, and ferroptosis in pancreatic and colon cancer cells, along with its modulation of the MAPK signaling pathway. MCL was found to substantially suppress cell viability in these cancer cells, particularly in MIA PaCa-2 and HT-29 cell lines. The study identified that MCL induced autophagy by enhancing the levels of autophagy markers such as Atg7, p-Beclin-1, and Beclin-1, which was attenuated by the autophagy inhibitor 3-MA. Furthermore, MCL was found to facilitate paraptosis, indicated by decreased Alix and in-creased ATF4 and CHOP levels. It also promoted ferroptosis, as demonstrated by the reduced expression of SLC7A11, elevated TFRC levels, and increased intracellular iron. Additionally, MCL activated the MAPK signaling pathway, marked by the phosphorylation of JNK, p38, and ERK, linked with an increase in ROS production that is vital in regulating these cell death mechanisms. These findings propose that MCL is a versatile anticancer agent, capable of activating various cell death pathways by modulating MAPK signaling and ROS levels. These results emphasize the therapeutic promise of MCL in treating cancer, pointing to the necessity of further in vivo investigations to confirm these effects and determine its potential clinical uses.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155654"},"PeriodicalIF":2.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472147","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}
Pub Date : 2024-10-11DOI: 10.1016/j.prp.2024.155650
Xianli Ju , Zhengzhuo Chen , Honglin Yan , Bin Luo , Fangrui Zhao , Aoling Huang , Xi Chen , Jingping Yuan
Purpose
This study aims to investigate the change of Ki67 value pre- and post-neoadjuvant therapy (NAT) and evaluate its potential value in predicting survival outcomes in different molecular subtypes of breast cancer.
Methods
A total of 257 breast cancer patients who underwent NAT at Renmin Hospital of Wuhan University from July 2019 to Sep 2023 were included in this study. The Ki67 index of the patients was re-interpreted by two attending physicians, and the changes of Ki67 value pre- and post-NAT were compared. Chi-square test (χ2) and logistic regression were conducted to examine the correlation between various characteristics and the efficacy of NAT. Disease-free survival (DFS) was calculated using the Kaplan-Meier curve and compared using the log-rank test.
Results
Patients with higher histological grade, negative expression of estrogen receptor (ER) or progesterone receptor (PR), positive expression of human epidermal growth receptor 2 (HER2), higher pretreatment Ki67 index, absence of lymph node metastasis, and those with HER2 positive and triple-negative breast cancer were associated with improved efficacy of NAT. Our study identified that the optimal cut-off value for the changes in Ki67 index pre- and post-NAT related to the effectiveness of NAT was “-88.19 %” in whole chort, which was related to the aforementioned clinical characteristics. Besides, the optimal cut-off values for the luminal, HER2-enriched and triple-negative subtypes were “-91.83 %”, “-46.12 %” and “-81.67 %”, respectively. Survival analysis demonstrated that the changes in Ki67 value were significantly associated with DFS in the HER2-enriched and triple-negative subtype, but not in the luminal subtype.
Conclusions
Preoperative clinicopathological features and changes in Ki67 value pre-and post-NAT can contribute to providing patients with a more accurate prognosis.
{"title":"Correlation analysis of Ki67 changes with survival outcomes in breast cancer before and after neoadjuvant therapy based on residual cancer Burden grade","authors":"Xianli Ju , Zhengzhuo Chen , Honglin Yan , Bin Luo , Fangrui Zhao , Aoling Huang , Xi Chen , Jingping Yuan","doi":"10.1016/j.prp.2024.155650","DOIUrl":"10.1016/j.prp.2024.155650","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to investigate the change of Ki67 value pre- and post-neoadjuvant therapy (NAT) and evaluate its potential value in predicting survival outcomes in different molecular subtypes of breast cancer.</div></div><div><h3>Methods</h3><div>A total of 257 breast cancer patients who underwent NAT at Renmin Hospital of Wuhan University from July 2019 to Sep 2023 were included in this study. The Ki67 index of the patients was re-interpreted by two attending physicians, and the changes of Ki67 value pre- and post-NAT were compared. Chi-square test (χ<sup>2</sup>) and logistic regression were conducted to examine the correlation between various characteristics and the efficacy of NAT. Disease-free survival (DFS) was calculated using the Kaplan-Meier curve and compared using the log-rank test.</div></div><div><h3>Results</h3><div>Patients with higher histological grade, negative expression of estrogen receptor (ER) or progesterone receptor (PR), positive expression of human epidermal growth receptor 2 (HER2), higher pretreatment Ki67 index, absence of lymph node metastasis, and those with HER2 positive and triple-negative breast cancer were associated with improved efficacy of NAT. Our study identified that the optimal cut-off value for the changes in Ki67 index pre- and post-NAT related to the effectiveness of NAT was “-88.19 %” in whole chort, which was related to the aforementioned clinical characteristics. Besides, the optimal cut-off values for the luminal, HER2-enriched and triple-negative subtypes were “-91.83 %”, “-46.12 %” and “-81.67 %”, respectively. Survival analysis demonstrated that the changes in Ki67 value were significantly associated with DFS in the HER2-enriched and triple-negative subtype, but not in the luminal subtype.</div></div><div><h3>Conclusions</h3><div>Preoperative clinicopathological features and changes in Ki67 value pre-and post-NAT can contribute to providing patients with a more accurate prognosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155650"},"PeriodicalIF":2.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433479","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}
Pub Date : 2024-10-11DOI: 10.1016/j.prp.2024.155653
Maryam Mahjoubin-Tehran , Ammar Hasan , Ali H. Eid , Wael Almahmeed , Prashant Kesharwani , Alexandra E. Butler , Tannaz Jamialahmadi , Amirhossein Sahebkar
Background
Curcumin, a ubiquitous polyphenol in turmeric, possesses many anti-cancer and anti-inflammatory properties. These therapeutic effects are largely resultant of curcumin’s ability to modulate global gene expression. Bioinformatics-based approaches for analyzing differential gene expression are effective tools in gaining a more profound understanding of the underlying mechanisms of action.
Aim
In this study, we aimed to identify key genes that were differentially regulated by curcumin treatment of mice.
Methods
We downloaded GSE10684 and GSE13705 microarray profiles from the GEO database. Differentially expressed genes were identified and compared in both data sets. Twenty-seven genes that are significantly differentially regulated in both datasets were considered as key genes.
Results
Gene ontology (GO) enrichment indicates these key genes were mostly enriched in GO Process of regulation of immune response and immune system process. The KEGG pathways of Cytokine-cytokine receptor interaction and TISSUES of Immune system were the top enriched terms of key genes base on strength and false discovery rate. The protein-protein interactions were analyzed by the STRING. PPI clustering showed that cluster 1 with Csf1, Cxcl16, Cxcr3, Fas, Il7r, Rassf2, and Rp2h was the most significant cluster. GO enrichment analysis for this cluster also showed the roles of these genes in immune system regulation.
Conclusions
Overall, the microarray datasets to identify the key genes and the related pathways which were affected by curcumin treatments show that curcumin has a significant impact on immune system regulation through the modulation of gene expression.
{"title":"Effects of dietary curcumin on gene expression: An analysis of transcriptomic data in mice","authors":"Maryam Mahjoubin-Tehran , Ammar Hasan , Ali H. Eid , Wael Almahmeed , Prashant Kesharwani , Alexandra E. Butler , Tannaz Jamialahmadi , Amirhossein Sahebkar","doi":"10.1016/j.prp.2024.155653","DOIUrl":"10.1016/j.prp.2024.155653","url":null,"abstract":"<div><h3>Background</h3><div>Curcumin, a ubiquitous polyphenol in turmeric, possesses many anti-cancer and anti-inflammatory properties. These therapeutic effects are largely resultant of curcumin’s ability to modulate global gene expression. Bioinformatics-based approaches for analyzing differential gene expression are effective tools in gaining a more profound understanding of the underlying mechanisms of action.</div></div><div><h3>Aim</h3><div>In this study, we aimed to identify key genes that were differentially regulated by curcumin treatment of mice.</div></div><div><h3>Methods</h3><div>We downloaded GSE10684 and GSE13705 microarray profiles from the GEO database. Differentially expressed genes were identified and compared in both data sets. Twenty-seven genes that are significantly differentially regulated in both datasets were considered as key genes.</div></div><div><h3>Results</h3><div>Gene ontology (GO) enrichment indicates these key genes were mostly enriched in GO Process of regulation of immune response and immune system process. The KEGG pathways of Cytokine-cytokine receptor interaction and TISSUES of Immune system were the top enriched terms of key genes base on strength and false discovery rate. The protein-protein interactions were analyzed by the STRING. PPI clustering showed that cluster 1 with <em>Csf1, Cxcl16, Cxcr3, Fas, Il7r, Rassf2,</em> and <em>Rp2h</em> was the most significant cluster. GO enrichment analysis for this cluster also showed the roles of these genes in immune system regulation.</div></div><div><h3>Conclusions</h3><div>Overall, the microarray datasets to identify the key genes and the related pathways which were affected by curcumin treatments show that curcumin has a significant impact on immune system regulation through the modulation of gene expression.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155653"},"PeriodicalIF":2.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472151","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}
Pub Date : 2024-10-11DOI: 10.1016/j.prp.2024.155616
Sumanta Das , Divya Gupta , Bheru Dan Charan , Saumya Sahu , Vaishali Suri , Ajay Garg , Vivek Tandon , Ashish Suri , Mehar Chand Sharma
Astroblastoma, a unique entity of glial tumor, predominantly occur in young women with distinctive MN1 rearrangement, Given its limited documentation in existing literature, we report eight cases of astroblastoma, detailing their clinical, radiological, and histopathological characteristics along with molecular analysis. We conducted a retrospective analysis of our neuropathology archive database spanning the past 8 years. We included all cases that underwent Magnetic Resonance Imaging (MRI), surgical resection, histopathological examination, molecular testing, and follow-up. Histopathological examination involving immunohistochemistry and Fluorescence In Situ Hybridization (FISH) was carried out for all cases. All tumors were found to be located in the supratentorial region (cerebral hemisphere). The median age of the group was 35.1 years, with a female-to-male ratio of 1.6:1. The most common clinical presentation was headache. Morphologically, all tumors exhibited astroblastic features with pseudorosettes and perivascular hyalinization. Immunohistochemistry consistently revealed positivity for EMA and variable immunoreactivity for GFAP, OLIG2, and D2–40. Fluorescence In Situ Hybridization (FISH) analysis conducted for all cases showed MN1 rearrangement in 7 cases. The mean follow-up period was 45 months (ranging from 12 to 105 months). Radiotherapy was administered for high-grade and recurrent astroblastomas. All patients are currently alive and in good health.
Astroblastomas are uncommon central nervous system (CNS) tumors with characteristics morphology and molecular signatures. They typically carry a favorable prognosis. High level suspicion is required for their diagnosis and molecular analysis is must to distinguish them from other morphological mimics.
{"title":"Astroblastoma: A molecularly defined entity, its clinico-radiological & pathological analysis of eight cases and review of literature","authors":"Sumanta Das , Divya Gupta , Bheru Dan Charan , Saumya Sahu , Vaishali Suri , Ajay Garg , Vivek Tandon , Ashish Suri , Mehar Chand Sharma","doi":"10.1016/j.prp.2024.155616","DOIUrl":"10.1016/j.prp.2024.155616","url":null,"abstract":"<div><div>Astroblastoma, a unique entity of glial tumor, predominantly occur in young women with distinctive MN1 rearrangement, Given its limited documentation in existing literature, we report eight cases of astroblastoma, detailing their clinical, radiological, and histopathological characteristics along with molecular analysis. We conducted a retrospective analysis of our neuropathology archive database spanning the past 8 years. We included all cases that underwent Magnetic Resonance Imaging (MRI), surgical resection, histopathological examination, molecular testing, and follow-up. Histopathological examination involving immunohistochemistry and Fluorescence In Situ Hybridization (FISH) was carried out for all cases. All tumors were found to be located in the supratentorial region (cerebral hemisphere). The median age of the group was 35.1 years, with a female-to-male ratio of 1.6:1. The most common clinical presentation was headache. Morphologically, all tumors exhibited astroblastic features with pseudorosettes and perivascular hyalinization. Immunohistochemistry consistently revealed positivity for EMA and variable immunoreactivity for GFAP, OLIG2, and D2–40. Fluorescence In Situ Hybridization (FISH) analysis conducted for all cases showed MN1 rearrangement in 7 cases. The mean follow-up period was 45 months (ranging from 12 to 105 months). Radiotherapy was administered for high-grade and recurrent astroblastomas. All patients are currently alive and in good health.</div><div>Astroblastomas are uncommon central nervous system (CNS) tumors with characteristics morphology and molecular signatures. They typically carry a favorable prognosis. High level suspicion is required for their diagnosis and molecular analysis is must to distinguish them from other morphological mimics.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155616"},"PeriodicalIF":2.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438328","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}
Pub Date : 2024-10-10DOI: 10.1016/j.prp.2024.155623
Gokcen Unal Kocabas , Asli Kisim Blatti , Afig Berdeli , Ahmet Gokhan Ozgen , Banu Sarer Yurekli
Background
Resveratrol, a herbal phytoalexin, is known to have anti-tumor effects in several tumors including thyroid cancer cells.
Aim
The aim of this study was to determine the effects of resveratrol on the expression of BRAF, ERK and NIS mRNA levels and protein expression in B-CPAP human thyroid papillary cancer cell line.
Methods
B-CPAP cells were treated with resveratrol at concentrations of 10–100 μM for 24–48–72 h. Cell viability was assessed by XTT Cell Proliferation Assay. BRAF, ERK and NIS mRNA levels were evaluated by rt-PCR method. Protein expressions were evaluated by Western Blot method.
Results
Resveratrol was found to inhibit cell proliferation in a time and dose dependent manner. The IC50 values of resveratrol were 18.7 μM and 56.8 μM after 48 h and 72 h respectively. Resveratrol treatment of B-CPAP cells resulted in up to 1.5-fold reduction in BRAF mRNA and up to 5.5 fold reduction in ERK mRNA levels. NIS mRNA levels showed up to 3-fold increase. Western Blot studies confirmed the rt- PCR results with a decrease in BRAF and ERK, and increase in NIS protein expressions.
Conclusion
This study demonstrated that resveratrol inhibits thyroid papillary carcinoma cell proliferation and reduces poor prognostic BRAF and ERK mRNA and protein expressions, while increasing NIS mRNA and protein expression suggesting a redifferentiating effect. More studies are needed to evaluate resveratrol as a novel therapeutic agent in the treatment of papillary thyroid cancer.
{"title":"MAPK pathway and NIS in B-CPAP human papillary thyroid carcinoma cells treated with resveratrol","authors":"Gokcen Unal Kocabas , Asli Kisim Blatti , Afig Berdeli , Ahmet Gokhan Ozgen , Banu Sarer Yurekli","doi":"10.1016/j.prp.2024.155623","DOIUrl":"10.1016/j.prp.2024.155623","url":null,"abstract":"<div><h3>Background</h3><div>Resveratrol, a herbal phytoalexin, is known to have anti-tumor effects in several tumors including thyroid cancer cells.</div></div><div><h3>Aim</h3><div>The aim of this study was to determine the effects of resveratrol on the expression of BRAF, ERK and NIS mRNA levels and protein expression in B-CPAP human thyroid papillary cancer cell line.</div></div><div><h3>Methods</h3><div>B-CPAP cells were treated with resveratrol at concentrations of 10–100 μM for 24–48–72 h. Cell viability was assessed by XTT Cell Proliferation Assay. BRAF, ERK and NIS mRNA levels were evaluated by rt-PCR method. Protein expressions were evaluated by Western Blot method.</div></div><div><h3>Results</h3><div>Resveratrol was found to inhibit cell proliferation in a time and dose dependent manner. The IC50 values of resveratrol were 18.7 μM and 56.8 μM after 48 h and 72 h respectively. Resveratrol treatment of B-CPAP cells resulted in up to 1.5-fold reduction in BRAF mRNA and up to 5.5 fold reduction in ERK mRNA levels. NIS mRNA levels showed up to 3-fold increase. Western Blot studies confirmed the rt- PCR results with a decrease in BRAF and ERK, and increase in NIS protein expressions.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that resveratrol inhibits thyroid papillary carcinoma cell proliferation and reduces poor prognostic BRAF and ERK mRNA and protein expressions, while increasing NIS mRNA and protein expression suggesting a redifferentiating effect. More studies are needed to evaluate resveratrol as a novel therapeutic agent in the treatment of papillary thyroid cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155623"},"PeriodicalIF":2.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434068","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}
Pub Date : 2024-10-10DOI: 10.1016/j.prp.2024.155646
Chenyu Qian , Yu Chen , Zihao Zhao , Yilin Hu , Jianfeng Yi , Shun Chen , Jiancheng He , Junjie Chen , Wanjiang Xue
Gastric cancer (GC) is a malignancy with a relatively high mortality rate. This study aimed to ascertain the prognostic significance of long non-coding RNA (lncRNA) AC010457.1 in GC and elucidate its role in disease progression. The Cancer Genome Atlas (TCGA) database was used to screen the prognosis-associated differentially expressed lncRNAs in GC patients. Kaplan-Meier curves, univariate and multivariate Cox regression analyses were applied to assess the prognostic significance of AC010457.1. In vitro and in vivo functional assays were performed to evaluate the effects of AC010457.1 on cellular proliferation and metastasis. Mechanistic investigations, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Western blotting (WB), Immunofluorescence (IF), and Immunohistochemistry (IHC), were used to explore the signaling pathways activated by AC010457.1. We demonstrated that AC010457.1 was abnormally upregulated in GC tissues, and that this aberrant upregulation was associated with a poor prognosis for GC patients. The functional experiments proved that the downregulated of AC010457.1 hindered GC cell proliferation, migration, and invasive potential. Furthermore, KEGG analysis revealed a significant association between AC010457.1 and the PI3K/AKT signaling pathway, which was further corroborated by WB analysis. Rescue experiments provided additional confirmation that AC010457.1 regulated PI3K/AKT promote GC proliferation, migration, and epithelial-mesenchymal transition (EMT). Collectively, our findings suggest that AC010457.1 overexpression serves as a distinct prognostic risk factor in GC and may represent a promising therapeutic target for the treatment of this malignancy.
{"title":"Long non-coding RNA AC010457.1 promotes the growth and EMT of gastric cancer via the PI3K/AKT axis","authors":"Chenyu Qian , Yu Chen , Zihao Zhao , Yilin Hu , Jianfeng Yi , Shun Chen , Jiancheng He , Junjie Chen , Wanjiang Xue","doi":"10.1016/j.prp.2024.155646","DOIUrl":"10.1016/j.prp.2024.155646","url":null,"abstract":"<div><div>Gastric cancer (GC) is a malignancy with a relatively high mortality rate. This study aimed to ascertain the prognostic significance of long non-coding RNA (lncRNA) AC010457.1 in GC and elucidate its role in disease progression. The Cancer Genome Atlas (TCGA) database was used to screen the prognosis-associated differentially expressed lncRNAs in GC patients. Kaplan-Meier curves, univariate and multivariate Cox regression analyses were applied to assess the prognostic significance of AC010457.1. In vitro and in vivo functional assays were performed to evaluate the effects of AC010457.1 on cellular proliferation and metastasis. Mechanistic investigations, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Western blotting (WB), Immunofluorescence (IF), and Immunohistochemistry (IHC), were used to explore the signaling pathways activated by AC010457.1. We demonstrated that AC010457.1 was abnormally upregulated in GC tissues, and that this aberrant upregulation was associated with a poor prognosis for GC patients. The functional experiments proved that the downregulated of AC010457.1 hindered GC cell proliferation, migration, and invasive potential. Furthermore, KEGG analysis revealed a significant association between AC010457.1 and the PI3K/AKT signaling pathway, which was further corroborated by WB analysis. Rescue experiments provided additional confirmation that AC010457.1 regulated PI3K/AKT promote GC proliferation, migration, and epithelial-mesenchymal transition (EMT). Collectively, our findings suggest that AC010457.1 overexpression serves as a distinct prognostic risk factor in GC and may represent a promising therapeutic target for the treatment of this malignancy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155646"},"PeriodicalIF":2.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505686","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}
Pub Date : 2024-10-09DOI: 10.1016/j.prp.2024.155649
Daohong Li , Yuwei Jin , Jinxing Hu , Hui He , Aixia Hu
Background
Accumulating studies have disclosed that circular RNAs (circRNAs) are closely associated with the malignant progression of colorectal cancer (CRC). The aim of our work was to reveal the function of circ_0038718 in CRC.
Methods
The level of genes and proteins were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. In vitro researches were executed via utilizing cell counting Kit-8 (CCK-8), EdU, flow cytometry analysis and wound-healing assay, individually. The target relationship was validated by Dual-luciferase reporter assay. In vivo assay was employed through establishing xenograft tumor model.
Results
Circ_0038718 was identified to be increased in CRC tissues and cells. Circ_0038718 downregulation suppressed cell proliferation, migration and facilitated apoptosis of CRC. Mechanistically, circ_0038718 could sponge miR-761 and miR-214–3p to modulate the expression of ITGA6. The rescue experiments proved that miR-761 or miR-214–3p inhibitor attenuated the repressive impact of circ_0038718 inhibition on CRC cells progression, and overexpressed ITGA6 could weaken the inhibitory effect of miR-761 or miR-214–3p on tumor cells. Furthermore, depletion of circ_0038718 confined the tumor growth in vivo.
Conclusion
Circ_0038718 aggravated the progression of CRC cells via mediating ITGA6 expression through targeting miR-761 and miR-214–3p, providing a new therapeutic target for CRC patients.
{"title":"Circ_0038718 augments colorectal cancer progression through mediating the miR-761/miR-214–3p/ITGA6 axis","authors":"Daohong Li , Yuwei Jin , Jinxing Hu , Hui He , Aixia Hu","doi":"10.1016/j.prp.2024.155649","DOIUrl":"10.1016/j.prp.2024.155649","url":null,"abstract":"<div><h3>Background</h3><div>Accumulating studies have disclosed that circular RNAs (circRNAs) are closely associated with the malignant progression of colorectal cancer (CRC). The aim of our work was to reveal the function of circ_0038718 in CRC.</div></div><div><h3>Methods</h3><div>The level of genes and proteins were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. <em>In vitro</em> researches were executed via utilizing cell counting Kit-8 (CCK-8), EdU, flow cytometry analysis and wound-healing assay, individually. The target relationship was validated by Dual-luciferase reporter assay. <em>In vivo</em> assay was employed through establishing xenograft tumor model.</div></div><div><h3>Results</h3><div>Circ_0038718 was identified to be increased in CRC tissues and cells. Circ_0038718 downregulation suppressed cell proliferation, migration and facilitated apoptosis of CRC. Mechanistically, circ_0038718 could sponge miR-761 and miR-214–3p to modulate the expression of ITGA6. The rescue experiments proved that miR-761 or miR-214–3p inhibitor attenuated the repressive impact of circ_0038718 inhibition on CRC cells progression, and overexpressed ITGA6 could weaken the inhibitory effect of miR-761 or miR-214–3p on tumor cells. Furthermore, depletion of circ_0038718 confined the tumor growth <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>Circ_0038718 aggravated the progression of CRC cells via mediating ITGA6 expression through targeting miR-761 and miR-214–3p, providing a new therapeutic target for CRC patients.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155649"},"PeriodicalIF":2.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434069","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}
Pub Date : 2024-10-09DOI: 10.1016/j.prp.2024.155648
Giuseppe G. Loscocco , Margherita Vannucchi , Raffaella Santi , Andrea Amorosi , Stefania Scarpino , Maria Chiara Siciliano , Paola Guglielmelli , Claudio Tripodo , Arianna Di Napoli , Alessandro M. Vannucchi
Hepatoid thymic carcinoma (HTC) is an extremely rare variant of primary epithelial tumor of the thymus morphologically resembling hepatocellular carcinoma Herein, we report an additional case of HTC diagnosed in a 40-years-old man affected by polycythemia vera and treated with ropeginterferon alfa 2-b, for the first time deeply analyzing the molecular profile of this distinctive thymic malignancy. By immunohistochemistry, tumor cells were positive for cytokeratin 7-19, GLUT1, and Hep-Par-1, whereas AFP tested negative. Whole exome sequencing revealed loss of function mutations in TP53, STK11, PBRM1, SMAD3, FN1, NTRK1, and FANCD2, as well as gain of function mutations in MTOR, BCL11A and COL1A1, along with amplification of CCND3 and MDM2. This mutational landscape halfway between thymic carcinoma (TP53, PBRM1) and hepatoid variant carcinoma of other sites (STK11) suggests that, at some point during carcinogenesis, a switch occurred from an epithelial thymic phenotype to a hepatoid-like one.
{"title":"Hepatoid Thymic Carcinoma in a Polycythemia Vera Patient Treated with Ropeginterferon Alfa-2b: Clinical, Histopathological and Molecular Correlates","authors":"Giuseppe G. Loscocco , Margherita Vannucchi , Raffaella Santi , Andrea Amorosi , Stefania Scarpino , Maria Chiara Siciliano , Paola Guglielmelli , Claudio Tripodo , Arianna Di Napoli , Alessandro M. Vannucchi","doi":"10.1016/j.prp.2024.155648","DOIUrl":"10.1016/j.prp.2024.155648","url":null,"abstract":"<div><div>Hepatoid thymic carcinoma (HTC) is an extremely rare variant of primary epithelial tumor of the thymus morphologically resembling hepatocellular carcinoma Herein, we report an additional case of HTC diagnosed in a 40-years-old man affected by polycythemia vera and treated with ropeginterferon alfa 2-b, for the first time deeply analyzing the molecular profile of this distinctive thymic malignancy. By immunohistochemistry, tumor cells were positive for cytokeratin 7-19, GLUT1, and Hep-Par-1, whereas AFP tested negative. Whole exome sequencing revealed loss of function mutations in <em>TP53</em>, <em>STK11, PBRM1, SMAD3</em>, <em>FN1</em>, <em>NTRK1,</em> and <em>FANCD2</em>, as well as gain of function mutations in <em>MTOR</em>, <em>BCL11A</em> and <em>COL1A1</em>, along with amplification of <em>CCND3</em> and <em>MDM2.</em> This mutational landscape halfway between thymic carcinoma (<em>TP53</em>, <em>PBRM1</em>) and hepatoid variant carcinoma of other sites (<em>STK11)</em> suggests that, at some point during carcinogenesis, a switch occurred from an epithelial thymic phenotype to a hepatoid-like one.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155648"},"PeriodicalIF":2.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419554","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}
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