Pathology, research and practice最新文献

{"title":"Impact of genetic variations of gene involved in regulation of metabolism, inflammation and coagulation on pathogenesis of cardiac injuries associated with COVID-19","authors":"","doi":"10.1016/j.prp.2024.155608","DOIUrl":"10.1016/j.prp.2024.155608","url":null,"abstract":"<div><h3>Background</h3><div>SARS-CoV-2 infection can result in long-term chronic cardiovascular (CV) damage after the acute phase of the illness. COVID-19 frequently causes active myocarditis, SARS-CoV-2 can directly infect and kill cardiac cells, causing severe pathology and dysfunction across the organs and cells. Till now, the pathogenesis of COVID-19-associated cardiac injuries has not been understood, but there are several factors that contribute to the progression of cardiac injuries, such as genetic, dietary, and environmental. Among them ranges of host genetic factor including metabolizing, inflammation, and coagulation related genes have a role to contribute the cardiac injuries induced by COVID-19. Hereditary DNA sequence variations contribute to the risk of illness in almost all of these diseases. Hence, we comprehended the occurrence of genetic variations of metabolizing, inflammation and coagulation-related genes in the general population, their expression in various diseases, and their impact on cardiac injuries induced by COVID-19.</div></div><div><h3>Method</h3><div>We utilized multiple databases, including PubMed (Medline), EMBASE, and Google Scholar, for literature searches.</div></div><div><h3>Description</h3><div>The genes involved in metabolism (<em>APOE, MTHFR),</em> coagulation <em>(PAI-1</em>, <em>ACE</em>2), and immune factors (CRP, ESR, and troponin I) may have a role in the progression of COVID-19-associated cardiac injuries. The risk factors for CVD are significantly varied between and within different regions. In healthy individuals, the <em>ACE I</em> allele is responsible for the predisposition to CAD, but the <em>ACE</em> D haplotype is responsible for susceptibility and severity, which ultimately leads to heart failure. Patients who carry the T allele of rs12329760 in the <em>TMPRSS2</em> gene are at risk for developing the severe form of COVID-19. <em>IL-6</em> (rs1800796/rs1800795) polymorphism is associated with an increased mortality rate and susceptibility to severe COVID-19 disease. While the putative role of <em>IL-6</em> associated with chronic, inflammatory diseases like cardiac and cerebrovascular disease is well known.</div></div><div><h3>Conclusion</h3><div>The occurrence of genetic variations in the <em>ACE-2</em>, <em>AGT, DPP-IV, TMPRSS2, FUIRN, IL-4, IL-6, IFN-γ,</em> and <em>CYP2D6</em> genes is varied among different populations. Examining the correlation between these variations and their protein levels and cardiac injuries induced by COVID-19 may provide valuable insights into the pathogenesis of cardiac injuries induced by COVID-19.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505684","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":"Gut-associated lymphoid tissue carcinoma analyzed using next-generation sequencing: A case report","authors":"","doi":"10.1016/j.prp.2024.155621","DOIUrl":"10.1016/j.prp.2024.155621","url":null,"abstract":"<div><div>Tumors related to the gut-associated lymphoid tissue (GALT) have been recently described. GALT carcinomas (GCs) have a characteristic appearance: macroscopically, they appear as a \"dome-type\" lesion, whereas microscopically, they show dilated cystic glands in the submucosa, differentiated adenocarcinoma without goblet cells, and stromal lymphocytes with germinal centers. However, their origin and pathogenesis remain controversial. Here, we present the case of a 54-year-old man that presented with a protruding lesion in the upper rectum during colonoscopy and had no family or past medical history. Low anterior resection was performed, and the tumor was diagnosed as GC based on its typical morphology. The tumor cells were negative for Mucin 2 and other mucins and CD10. p53 showed null-type. The tumor was associated with rich lymphocyte infiltration and germinal centers. Next-generation sequencing detected <em>EGFR</em> missense and <em>TP53</em> nonsense mutations. Although GCs are known as conventional colorectal carcinomas that invade the submucosa, this case showed no neoplastic lesion in the mucosal epithelium in situ. Moreover, we detected <em>EGFR</em> and <em>TP53</em> mutations (no pathogenic <em>APC</em> or <em>KRAS</em> mutations), which are not conventional adenoma-carcinoma mutations. Further studies are warranted to confirm whether GC is a sporadic carcinoma that invades the GALT submucosa.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372496","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":"Machine learning algorithms and biomarkers identification for pancreatic cancer diagnosis using multi-omics data integration","authors":"","doi":"10.1016/j.prp.2024.155602","DOIUrl":"10.1016/j.prp.2024.155602","url":null,"abstract":"<div><h3>Purpose</h3><div>Pancreatic cancer is a lethal type of cancer with most of the cases being diagnosed in an advanced stage and poor prognosis. Developing new diagnostic and prognostic markers for pancreatic cancer can significantly improve early detection and patient outcomes. These biomarkers can potentially revolutionize medical practice by enabling personalized, more effective, targeted treatments, ultimately improving patient outcomes.</div></div><div><h3>Methods</h3><div>The search strategy was developed following PRISMA guidelines. A comprehensive search was performed across four electronic databases: PubMed, Scopus, EMBASE, and Web of Science, covering all English publications up to September 2022. The Newcastle-Ottawa Scale (NOS) was utilized to assess bias, categorizing studies as \"good,\" \"fair,\" or \"poor\" quality based on their NOS scores. Descriptive statistics for all included studies were compiled and reviewed, along with the NOS scores for each study to indicate their quality assessment.</div></div><div><h3>Results</h3><div>Our results showed that SVM and RF are the most widely used algorithms in machine learning and data analysis, particularly for biomarker identification. SVM, a supervised learning algorithm, is employed for both classification and regression by mapping data points in high-dimensional space to identify the optimal separating hyperplane between classes.</div></div><div><h3>Conclusions</h3><div>The application of machine-learning algorithms in the search for novel biomarkers in pancreatic cancer represents a significant advancement in the field. By harnessing the power of artificial intelligence, researchers are poised to make strides towards earlier detection and more effective treatment, ultimately improving patient outcomes in this challenging disease</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366153","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":"PARP inhibitors in ovarian cancer: Mechanisms, resistance, and the promise of combination therapy","authors":"","doi":"10.1016/j.prp.2024.155617","DOIUrl":"10.1016/j.prp.2024.155617","url":null,"abstract":"<div><div>Current approaches to treating ovarian cancer focus mainly on surgical cytoreduction and chemotherapy using platinum-based drugs, while newer methods such as immunotherapy are being investigated to enhance treatment outcomes. Treating ovarian cancer is complicated by challenges such as late-stage detection, tumor diversity, and limited treatment choices. Therefore, innovative strategies such as precision medicine and targeted therapies like PARPi (Poly ADP-Ribose Polymerase inhibitors) are increasingly necessary. The article highlights the significance of an innovative therapeutic approach focusing on PARPi in revolutionizing ovarian cancer treatment and improving patient outcomes. It covers the basic knowledge of PARP, its structure, and its function in DNA repair. It further emphasizes how inhibiting PARP can help in treating ovarian cancer. It elaborates on the mechanism of action of PARPi. It covers the clinical trials governing PARPi and the combination of drugs used with PARPi. It mentions how the resistance is developed to PARPi and the strategies to overcome the resistance developed.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366156","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":"Exploring mutations: GNAS and CDC73 in jaw fibroosseous lesions","authors":"","doi":"10.1016/j.prp.2024.155624","DOIUrl":"10.1016/j.prp.2024.155624","url":null,"abstract":"<div><h3>Introduction</h3><div>Benign fibro-osseous lesions have long been an area of diagnostic difficulty due to overlapping of histological and radiological features. Differentiating between these lesions is crucial because of their unique pathogenesis and biological behavior. Ossifying fibroma (OF) and fibrous dysplasia (FD) are the most prevalent lesions. However, not all FD or OF exhibit the typical radiological and histopathological features. In such situations, molecular-level investigations could be essential for precise identification and differentiation.</div></div><div><h3>Aim</h3><div>To evaluate the screening of GNAS and CDC73 mutations in blood and formalin fixed tumor tissues (FFTT) of FD and OF cases.</div></div><div><h3>Material and methods</h3><div>Six blood samples (three cases of FD and JOF each) and thirteen FFTT (six cases of FD and seven cases of JOF) were included in the study. DNA was extracted from peripheral blood samples using salting out method followed by whole exome sequencing. Multiple efforts were made to extract DNA from tumor tissues using various protocols, but no measurable yield was obtained.</div></div><div><h3>Results</h3><div>DNA derived from blood samples gave successful DNA library preparation and subsequent exome sequencing data generation. We report a pathogenic GNAS mutation (exon8:c.G602A:p.R201H) associated with McCune-Albright syndrome and a novel benign mutation identified in a case of FD (GNAS(NM_000516.7):c.257+687_257+688del) whereas none of the subjects of JOF displayed GNAS and/or CDC73 mutation.</div></div><div><h3>Conclusion</h3><div>Study observed mutations in GNAS gene in blood samples from FD cases. However, a limitation is that only DNA extracted from blood underwent successful exome sequencing. Potential reason for low-quality DNA extraction from tissue may be attributed to prior fixation procedures conducted on bone specimens.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366141","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":"Recent update on IGF-1/IGF-1R signaling axis as a promising therapeutic target for triple-negative breast cancer","authors":"","doi":"10.1016/j.prp.2024.155620","DOIUrl":"10.1016/j.prp.2024.155620","url":null,"abstract":"<div><div>Insulin-like growth factor 1/Insulin-like growth factor 1-receptor (IGF-1/IGF-1R) pathway is highly breast cancer subtype context-dependent. Triple-negative breast cancer (TNBC) is an aggressive, highly metastatic cancer showing early recurrence and poor prognosis. High expression of IGF-1 and its receptor IGF-1R, their interaction, autophosphorylation, and activation of intracellular signaling cascades have been significantly associated with TNBC pathophysiology. In the last five to seven years, marvelous work has been done to explore the role of IGF-1/IGF-1R axis in TNBC. In the present review, starting from the general introduction to IGF-1/IGF-1R pathway an up-to-date discussion was focused on its role in TNBC pathophysiology. Further we discussed the up/down stream molecular events of IGF-1/IGF-1R axis, clinical relevance of IGF-1 and IGF-1R levels in TNBC patients, anti-TNBC therapy and possible way-out for IGF-1/IGF-1R axis mediate therapy resistance in TNBC. Combination therapy strategy has been researched to overcome direct IGF-1/IGF-1R pathway inhibition mediated therapy resistance and produced promising results in the management of TNBC. The understanding of up/downstream of the IGF-1/IGF-1R axis provide immense focus on the pathway as a therapeutic target. It is expected within the next decade to determine its potentiality, or lack thereof, for TNBC treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366159","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":"Therapeutic approaches to microglial dysfunction in Alzheimer's disease: Enhancing phagocytosis and metabolic regulation","authors":"","doi":"10.1016/j.prp.2024.155614","DOIUrl":"10.1016/j.prp.2024.155614","url":null,"abstract":"<div><div>Microglia are essential in neurogenesis, synaptic pruning, and homeostasis. Nevertheless, aging, and cellular senescence may modify their role, causing them to shift from being shields to being players of neurodegeneration. In the aging brain, the population of microglia increases, followed by enhanced activity of genes related to neuroinflammation. This change increases their ability to cause inflammation, resulting in a long-lasting state of inflammation in the brain that harms the condition of neurons. In Alzheimer’s Disease (AD), microglia are located inside amyloid plaques and exhibit an inflammatory phenotype characterized by a diminished ability to engulf and remove waste material, worsening the illness's advancement. Genetic polymorphisms in TREM2, APOE, and CD33 highlight the significant impact of microglial dysfunction in AD. This review examines therapeutic approaches that aim to address microglial dysfunction, such as enhancing the microglial capability to engulf and remove amyloid-β clumps and regulating microglial metabolism and mitochondrial activity. Microglial transplanting and reprogramming advancements show the potential to restore their ability to reduce inflammation. Although there has been notable advancement, there are still voids in our knowledge of microglial biology, including their relationships with other brain cells. Further studies should prioritize the improvement of human AD models, establish standardized methods for characterizing microglia, and explore how various factors influence microglial responses. It is essential to tackle these problems to create effective treatment plans that focus on reducing inflammation in the brain and protecting against damage in age-related neurodegenerative illnesses.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351730","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":"A review on tyrosine kinase inhibitors for targeted breast cancer therapy","authors":"","doi":"10.1016/j.prp.2024.155607","DOIUrl":"10.1016/j.prp.2024.155607","url":null,"abstract":"<div><div>Breast cancer is a heterogeneous disease with complex molecular pathogenesis. Overexpression of several tyrosine kinase receptors is associated with poor prognosis, therefore, they can be key targets in breast cancer therapy. Tyrosine kinase inhibitors (TKIs) have emerged as leading agents in targeted cancer therapy due to their effectiveness in disrupting key molecular pathways involved in tumor growth. TKIs target various tyrosine kinases, including the human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), Vascular endothelial growth factor receptor (VEGFR), anaplastic lymphoma kinase (ALK), vascular endothelial growth factor receptor (VEGFR)-associated multi-targets, rearranged during transfection (RET), fibroblast growth factor receptor (FGFR), receptor tyrosine kinase-like orphan signal 1 (ROS1), Mitogen-activated protein kinase (MAPK), and tropomyosin receptor kinase (TRK). These drugs target the tyrosine kinase domain of receptor tyrosine kinases and play a vital role in proliferation and migration of breast cancer cells. Several TKIs, including lapatinib, neratinib, and tucatinib, have been developed and are currently used in clinical settings, often in combination with chemotherapy, endocrine therapy, or other targeted agents. TKIs have demonstrated remarkable benefits in enhancing progression-free and overall survival in patients with breast cancer and have become a standard of care for this population. This review provides an overview of TKIs currently being examined in preclinical studies and clinical trials, especially in combination with drugs approved for breast cancer treatment. TKIs have emerged as a promising therapeutic option for patients with breast cancer and hold potential for treating other breast cancer subtypes. The development of new TKIs and their integration into personalized treatment strategies will continue to shape the future of breast cancer therapy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322764","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":"Gastric-type extremely well-differentiated adenocarcinoma of the stomach: A rare tumor with diagnostic difficulties and high inter-observer variation in endoscopic pinch biopsies","authors":"","doi":"10.1016/j.prp.2024.155599","DOIUrl":"10.1016/j.prp.2024.155599","url":null,"abstract":"<div><div>Extremely well-differentiated gastric-type adenocarcinoma (EWDGA) is a rare type of gastric cancer composed of deceptively bland-looking malignant cells resembling normal foveolar or pyloric epithelium. The histological features of this tumor have not been recognized by many pathologists, and inter-observer variation studies are lacking. Here, we report seven EWDGAs and inter-observer variation of six preoperative biopsies was evaluated by 11 pathologists in a single institute. Based on the pathological diagnosis of the endoscopic biopsy slides, the average rate of definite malignancy diagnosis was 15.2 %, and the overall diagnostic concordance rate was 34.9 % among 11 pathologists. Microscopically, the surface epithelium was preserved and only a few atypical tumor glands were scattered in most endoscopic biopsies. Structural atypia was minimal, and the tumor glands were barely distinguishable from normal glands. Although nuclear atypia was minimal, enlarged nuclei, relatively large glands with irregular shapes, and abundant cytoplasmic mucin were observed in gastric pinch biopsies. In preoperative biopsies, no cases showed p53 overexpression, and Ki-67 labeling index ranged from 3 % to 35 % and was higher compared to non-neoplastic glands in 3 cases. After gastrectomy, four (57.1 %) patients had advanced gastric cancer and three (42.9 %) had lymph node metastasis. Genomic profiling of the four patients revealed mutations of <em>TP53</em>, <em>BRAF</em>, <em>KRAS</em>, <em>STK11</em>, and <em>MDM2/CCND1</em> amplification. Immunohistochemistry for p53 was not helpful while Ki-67 may be helpful when staining pattern is distinct from the non-neoplastic mucosa. In conclusion, it is challenging to diagnose EWDGA using biopsy specimens. Recognizing and addressing this rare entity will increase diagnostic accuracy to ensure the early diagnosis of cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372495","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":"Unveiling four axes ADAMTS9-AS2|MEG3/hsa-miR-150/PRKCA|MMP14 within prostate cancer through establishment of the ceRNA network","authors":"","doi":"10.1016/j.prp.2024.155604","DOIUrl":"10.1016/j.prp.2024.155604","url":null,"abstract":"<div><div>Prostate cancer is among the most common cancers in males. Recent application of system biology methods has resulted in identification of key genes in the process of carcinogenesis. In the current study, we selected two datasets related to prostate cancer (PCa) and performed bulk RNA-seq analysis by selecting samples with Gleason scores greater than 7 and combining them. Subsequently, using several systems biology approaches, we constructed the ceRNA network and ultimately identified key axes related to PCa. Our analyses revealed importance of ADAMTS9-AS2/miR-150/PRKCA, ADAMTS9-AS2/miR-150/MMP14, MEG3/miR-150/PRKCA and MEG3/miR-150/MMP14 with miR-150 being a central component. Remarkably, miR-150 exhibited strong statistical significance in survival analyses. Further, analyzing expression levels from TCGA datasets, the expression of the identified genes associates significantly with prostate cancer compared to normal tissue confirming the bioinformatic analyses. Therefore, these genes can be regarded as prognostic markers in prostate cancer and the pathways are potential targets for therapeutic interventions.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322765","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}