Pub Date : 2024-09-25DOI: 10.1016/j.prp.2024.155610
The high mortality rate of colorectal cancer (CRC) highlights the need for new treatment strategies; however, the venous invasion mechanisms in tumor endothelial cells within CRC remain unexplored. Therefore, we investigated the clinicopathological features of SRY-box transcription factor 17 (SOX17) in CRC. Immunohistochemical staining was performed on 55 CRC tissue specimens using a SOX17-specific antibody, followed by Kaplan–Meier and Cox proportional hazards regression analyses. SOX17 immunoreactivity was detected in the endothelial cells of tumor-penetrating vessels in 35/55 CRC samples. Kaplan–Meier analysis indicated that patients with SOX17 immunoreactivity had favorable overall and progression-free survival (log-rank test, P = 0.03 and 0.02, respectively). Notably, tumor endothelial SOX17 immunoreactivity was associated with a favorable prognosis in patients with stage III or IV disease (OS, P = 0.0089; PFS, P = 0.0065). Cox proportional hazard regression analysis indicated that SOX17 immunoreactivity is an independent factor for predicting favorable overall and progression-free survival in CRC (P = 0.02 and 0.01, respectively). The present findings suggest that SOX17 expression in tumor endothelial cells is a potential indicator of favorable prognosis in patients with CRC.
{"title":"SOX17 expression in tumor endothelial cells in colorectal cancer and its association with favorable outcomes in patients","authors":"","doi":"10.1016/j.prp.2024.155610","DOIUrl":"10.1016/j.prp.2024.155610","url":null,"abstract":"<div><div>The high mortality rate of colorectal cancer (CRC) highlights the need for new treatment strategies; however, the venous invasion mechanisms in tumor endothelial cells within CRC remain unexplored. Therefore, we investigated the clinicopathological features of SRY-box transcription factor 17 (SOX17) in CRC. Immunohistochemical staining was performed on 55 CRC tissue specimens using a SOX17-specific antibody, followed by Kaplan–Meier and Cox proportional hazards regression analyses. SOX17 immunoreactivity was detected in the endothelial cells of tumor-penetrating vessels in 35/55 CRC samples. Kaplan–Meier analysis indicated that patients with SOX17 immunoreactivity had favorable overall and progression-free survival (log-rank test, <em>P</em> = 0.03 and 0.02, respectively). Notably, tumor endothelial SOX17 immunoreactivity was associated with a favorable prognosis in patients with stage III or IV disease (OS, <em>P</em> = 0.0089; PFS, <em>P</em> = 0.0065). Cox proportional hazard regression analysis indicated that SOX17 immunoreactivity is an independent factor for predicting favorable overall and progression-free survival in CRC (<em>P</em> = 0.02 and 0.01, respectively). The present findings suggest that SOX17 expression in tumor endothelial cells is a potential indicator of favorable prognosis in patients with CRC.</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":"142351729","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 : 2024-09-25DOI: 10.1016/j.prp.2024.155611
Cancer continues to threaten human health regardless of novel therapeutic options. Over the last two decades, targeted therapy has emerged as a significant advancement in treating malignancies, surpassing standard chemoradiotherapy and surgical procedures. Gynecological malignancies, including cervical, endometrial, and ovarian carcinoma, have a bad prognosis in advanced or metastatic stages and are difficult to treat. The advancements in understanding the molecular pathways behind cancer development offer valuable insights into promising targeted medicines, and researchers have always searched for a superior and safe technique to target cancer-related oncoproteins because of the limited therapeutic benefit, drug resistance, and off-target effects of current targeted treatments. Recently, proteolysis-targeting chimeras (PROTACs) have been developed to selectively degrade proteins using the natural ubiquitin-proteasome system (UPS). These approaches have garnered significant attention in the field of cancer research. The rapid progress in PROTACs has also eased the targeting of various oncoproteins in gynecological cancer. Therefore, this review aims to elucidate the mechanism and research advancements of PROTACs and provide a comprehensive overview of their use in gynecological tumors.
{"title":"PROTACs in gynecological cancers: Current knowledge and future potential as a treatment strategy","authors":"","doi":"10.1016/j.prp.2024.155611","DOIUrl":"10.1016/j.prp.2024.155611","url":null,"abstract":"<div><div>Cancer continues to threaten human health regardless of novel therapeutic options. Over the last two decades, targeted therapy has emerged as a significant advancement in treating malignancies, surpassing standard chemoradiotherapy and surgical procedures. Gynecological malignancies, including cervical, endometrial, and ovarian carcinoma, have a bad prognosis in advanced or metastatic stages and are difficult to treat. The advancements in understanding the molecular pathways behind cancer development offer valuable insights into promising targeted medicines, and researchers have always searched for a superior and safe technique to target cancer-related oncoproteins because of the limited therapeutic benefit, drug resistance, and off-target effects of current targeted treatments. Recently, proteolysis-targeting chimeras (PROTACs) have been developed to selectively degrade proteins using the natural ubiquitin-proteasome system (UPS). These approaches have garnered significant attention in the field of cancer research. The rapid progress in PROTACs has also eased the targeting of various oncoproteins in gynecological cancer. Therefore, this review aims to elucidate the mechanism and research advancements of PROTACs and provide a comprehensive overview of their use in gynecological tumors.</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":"142366157","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 : 2024-09-25DOI: 10.1016/j.prp.2024.155612
Cervical cancer, originating from the epithelial tissue of the uterine cervix, constitutes the most commonly diagnosed malignancy among women worldwide. The predominant etiological factor underpinning cervical carcinogenesis is persistent infection with high-risk human papillomavirus (HPV) genotypes, notably HPV-16 and HPV-18. Oncoproteins encoded by high-risk HPV interfere with multiple essential cellular signaling cascades. Specifically, E5, E6, and E7 proteins disrupt the signaling pathways like p53, retinoblastoma tumor suppressor protein (pRB), The phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK), and Wnt/β-catenin, promoting HPV-mediated carcinogenesis. This dysregulation disrupts cell cycle control, apoptosis, and metastasis through modulation of microRNAs (miRNA) and key cellular processes. The novel therapeutic interventions for HPV prevention and detection are fundamental to patient management. RNA-based treatment modalities offer the potential for manipulating critical pathways involved in cervical carcinogenesis. RNA therapeutics offer novel approaches to drug development by targeting intracellular genetic elements inaccessible to conventional modalities. Additional advantages include rapid design, synthesis, and a reduced genotoxic profile compared to DNA-based therapies. Despite beneficial attributes, system stability and efficient delivery remain critical parameters. This study assessed the intricate relationship between HPV, cervical cancer, and various signaling pathways. The study explores miRNAs' diagnostic and therapeutic potential, mall interfering RNAs (siRNAs), and long non-coding RNAs (lncRNAs)in cervical cancer management. The review highlights the prospect of RNA-targeted therapies to modulate specific cancer signaling pathways. This approach offers a novel strategy for cervical cancer treatment through precise regulation of cancer signaling. Future research should concentrate on developing RNA-targeted interventions to improve cervical cancer treatment outcomes through increased therapeutic efficacy and specificity.
{"title":"Signaling pathways in HPV-induced cervical cancer: Exploring the therapeutic promise of RNA modulation","authors":"","doi":"10.1016/j.prp.2024.155612","DOIUrl":"10.1016/j.prp.2024.155612","url":null,"abstract":"<div><div>Cervical cancer, originating from the epithelial tissue of the uterine cervix, constitutes the most commonly diagnosed malignancy among women worldwide. The predominant etiological factor underpinning cervical carcinogenesis is persistent infection with high-risk human papillomavirus (HPV) genotypes, notably HPV-16 and HPV-18. Oncoproteins encoded by high-risk HPV interfere with multiple essential cellular signaling cascades. Specifically, E5, E6, and E7 proteins disrupt the signaling pathways like p53, retinoblastoma tumor suppressor protein (pRB), The phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK), and Wnt/β-catenin, promoting HPV-mediated carcinogenesis. This dysregulation disrupts cell cycle control, apoptosis, and metastasis through modulation of microRNAs (miRNA) and key cellular processes. The novel therapeutic interventions for HPV prevention and detection are fundamental to patient management. RNA-based treatment modalities offer the potential for manipulating critical pathways involved in cervical carcinogenesis. RNA therapeutics offer novel approaches to drug development by targeting intracellular genetic elements inaccessible to conventional modalities. Additional advantages include rapid design, synthesis, and a reduced genotoxic profile compared to DNA-based therapies. Despite beneficial attributes, system stability and efficient delivery remain critical parameters. This study assessed the intricate relationship between HPV, cervical cancer, and various signaling pathways. The study explores miRNAs' diagnostic and therapeutic potential, mall interfering RNAs (siRNAs), and long non-coding RNAs (lncRNAs)in cervical cancer management. The review highlights the prospect of RNA-targeted therapies to modulate specific cancer signaling pathways. This approach offers a novel strategy for cervical cancer treatment through precise regulation of cancer signaling. Future research should concentrate on developing RNA-targeted interventions to improve cervical cancer treatment outcomes through increased therapeutic efficacy and specificity.</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":"142366160","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 : 2024-09-25DOI: 10.1016/j.prp.2024.155609
Crystal-storing histiocytosis is a rare entity due to tumorous deposits of histiocytes containing crystalline inclusions, which in a majority of cases are made of immunoglobulins associated with lymphoproliferative disorders, although association with non-neoplastic disorders has also been reported. The histiocytes may be so abundant to obscure the underlying lymphoplasmacytic neoplasm. On the other hand, the Gaucher-like histiocytes might lead to a misinterpretation of granulomatous inflammation or storage disease. Herein, this case study reported clinical, pathological and next generation sequencing (NGS) features of a case of kappa chain myeloma with Gaucher-like crystal-storing histiocytosis in the bone marrow (BM). The methodology included BM aspiration and biopsy, immunohistochemistry, electron microscopy and NGS study by TruSight Oncology 500. Morphologically, the BM smear showed dense infiltration of sea blue histiocytes and atypical plasma cells with rhomboid crystals in cytoplasm. The BM biopsy showed excessive plasmacytic aggregates and dense histiocytic infiltrates with wrinkled paper-like or needle shaped cytoplasm. These plasma cells were positive for CD138 and showed lambda chain restriction. Electron microscopy highlighted the long rhomboid crystals with distinct periodicity consistent with crystalline immunoglobulins in the histiocytes. In addition, the NGS study from the BM aspiration specimen revealed PARP1, MSH6, KDR, CCND3 and STK11 mutations, which might be associated with inferior survival of myeloma patients. Accordingly, this case died of pneumonia with septic shock during treatment. Our findings suggest that the presence of rhomboid crystals in bone marrow smears may alert pathologists to look for the possibility of crystal-storing histiocytosis and the prognosis of patients with multiple myeloma may depend on the genetic features of tumor cells rather than the association with crystal-storing histiocytosis.
{"title":"Gaucher-like crystal-storing histiocytosis associated with kappa chain myeloma: A case report with next generation sequencing study","authors":"","doi":"10.1016/j.prp.2024.155609","DOIUrl":"10.1016/j.prp.2024.155609","url":null,"abstract":"<div><div>Crystal-storing histiocytosis is a rare entity due to tumorous deposits of histiocytes containing crystalline inclusions, which in a majority of cases are made of immunoglobulins associated with lymphoproliferative disorders, although association with non-neoplastic disorders has also been reported. The histiocytes may be so abundant to obscure the underlying lymphoplasmacytic neoplasm. On the other hand, the Gaucher-like histiocytes might lead to a misinterpretation of granulomatous inflammation or storage disease. Herein, this case study reported clinical, pathological and next generation sequencing (NGS) features of a case of kappa chain myeloma with Gaucher-like crystal-storing histiocytosis in the bone marrow (BM). The methodology included BM aspiration and biopsy, immunohistochemistry, electron microscopy and NGS study by TruSight Oncology 500. Morphologically, the BM smear showed dense infiltration of sea blue histiocytes and atypical plasma cells with rhomboid crystals in cytoplasm. The BM biopsy showed excessive plasmacytic aggregates and dense histiocytic infiltrates with wrinkled paper-like or needle shaped cytoplasm. These plasma cells were positive for CD138 and showed lambda chain restriction. Electron microscopy highlighted the long rhomboid crystals with distinct periodicity consistent with crystalline immunoglobulins in the histiocytes. In addition, the NGS study from the BM aspiration specimen revealed <em>PARP1, MSH6, KDR, CCND3</em> and <em>STK11</em> mutations, which might be associated with inferior survival of myeloma patients. Accordingly, this case died of pneumonia with septic shock during treatment. Our findings suggest that the presence of rhomboid crystals in bone marrow smears may alert pathologists to look for the possibility of crystal-storing histiocytosis and the prognosis of patients with multiple myeloma may depend on the genetic features of tumor cells rather than the association with crystal-storing histiocytosis.</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":"142366151","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 : 2024-09-25DOI: 10.1016/j.prp.2024.155606
For the past 3–4 decades, the discovery of Sanger’s method of pyrosequencing was the only method unparalleled till 2005 being employed as a method of whole genome sequencing (WGS). Following this, a revolutionary extensive parallel sequencing method, Next Generation Sequencing (NGS), was engineered. NGS supported a substantial number of bases under a high throughput metagenomic interrogation. Bioinformatics contributed notably to this advancement. It provided alignment tools, assembly algorithms, and protocols such as Illumina and hybridization capture which have metamorphosed clinical and translational diagnostics. With the extension in precision medicine and targeted therapy under NGS sectors such as epigenetics, transcriptomics, mutation detection, prognosis, therapeutics, and patient management have been gaining progress. Using NGS in real-time clinical settings has been proven to produce positive outcomes. The most recent instrumental benefaction of NGS has been decoding the SARS-CoV-2 virus epidemiology with the assistance of multiplex PCR. So far, it had been employed to inspect different levels of viral loads from low to mid. This has been executed by amplification and phylogenetic examination of the load to raise a connective link with the evolutionary history leading up to the period of origin. The depletion in the consumed time and extensive genome size under analysis was further coupled by a cutback in the cost of sequencing while executing NGS. With the aid of this review paper, we aspire to manifest how the above-mentioned elements have boosted, tissue, microbial, and molecular data interrogation. Along with this, promoting, and stimulating an extensive evaluation and expansion in the paradigm of morphological and phenotypic study, via bioinformatics can facilitate further advancement in personalized and concise clinical research.
{"title":"Next Generation Sequencing: Latent applications in clinical diagnostics with the advent of bioinformatic frameworks","authors":"","doi":"10.1016/j.prp.2024.155606","DOIUrl":"10.1016/j.prp.2024.155606","url":null,"abstract":"<div><div>For the past 3–4 decades, the discovery of Sanger’s method of pyrosequencing was the only method unparalleled till 2005 being employed as a method of whole genome sequencing (WGS). Following this, a revolutionary extensive parallel sequencing method, Next Generation Sequencing (NGS), was engineered. NGS supported a substantial number of bases under a high throughput metagenomic interrogation. Bioinformatics contributed notably to this advancement. It provided alignment tools, assembly algorithms, and protocols such as Illumina and hybridization capture which have metamorphosed clinical and translational diagnostics. With the extension in precision medicine and targeted therapy under NGS sectors such as epigenetics, transcriptomics, mutation detection, prognosis, therapeutics, and patient management have been gaining progress. Using NGS in real-time clinical settings has been proven to produce positive outcomes. The most recent instrumental benefaction of NGS has been decoding the SARS-CoV-2 virus epidemiology with the assistance of multiplex PCR. So far, it had been employed to inspect different levels of viral loads from low to mid. This has been executed by amplification and phylogenetic examination of the load to raise a connective link with the evolutionary history leading up to the period of origin. The depletion in the consumed time and extensive genome size under analysis was further coupled by a cutback in the cost of sequencing while executing NGS. With the aid of this review paper, we aspire to manifest how the above-mentioned elements have boosted, tissue, microbial, and molecular data interrogation. Along with this, promoting, and stimulating an extensive evaluation and expansion in the paradigm of morphological and phenotypic study, via bioinformatics can facilitate further advancement in personalized and concise clinical research.</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":"142366155","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 : 2024-09-24DOI: 10.1016/j.prp.2024.155600
Rapidly progressing ALL, a potentially fatal disease, demands timely diagnosis and treatment. On the other hand, spontaneous remission/regression (SR) is reported in various cancers including aggressive tumors like ALL. Infection or trauma-mediated immune system activation is assumed to cause SR, with the duration in cases of ALL typically being short. Indolent T-lymphoblastic proliferation (i-TLP) exhibits the uniform proliferation of TdT-positive T-cells, despite being a non-neoplastic disease, underscoring the significance of distinguishing it from T-cell acute lymphoblastic leukemia (T-ALL). i-TLP is expected to gain wider recognition and further advancements in understanding its pathology. Here, we present the case of a 59-year-old woman with T-ALL characterized by cycles of progression and SR followed by a rapid blast proliferation. This is the first reported case of T-ALL with repeated SR for more than one year, making this case an extremely rare clinical presentation. This challenging case will enhance comprehension of T-cell tumor pathogenesis.
进展迅速的 ALL 是一种可能致命的疾病，需要及时诊断和治疗。另一方面，各种癌症包括侵袭性肿瘤（如 ALL）都有自发性缓解/消退（SR）的报道。感染或创伤介导的免疫系统激活被认为是导致自发性缓解的原因，在 ALL 病例中，自发性缓解的持续时间通常很短。惰性T淋巴细胞增生（i-TLP）表现为TdT阳性T细胞的均匀增生，尽管它是一种非肿瘤性疾病，强调了将其与T细胞急性淋巴细胞白血病（T-ALL）区分开来的重要性。在此，我们介绍了一例59岁女性T-ALL患者的病例，其特征是进展和SR周期，随后是快速的囊泡增殖。这是首例反复出现 SR 超过一年的 T-ALL 病例，临床表现极为罕见。这一具有挑战性的病例将加深对 T 细胞肿瘤发病机制的理解。
{"title":"T-ALL presenting with i-TLP-like indolent clinical course with repeated spontaneous regressions","authors":"","doi":"10.1016/j.prp.2024.155600","DOIUrl":"10.1016/j.prp.2024.155600","url":null,"abstract":"<div><div>Rapidly progressing ALL, a potentially fatal disease, demands timely diagnosis and treatment. On the other hand, spontaneous remission/regression (SR) is reported in various cancers including aggressive tumors like ALL. Infection or trauma-mediated immune system activation is assumed to cause SR, with the duration in cases of ALL typically being short. Indolent T-lymphoblastic proliferation (i-TLP) exhibits the uniform proliferation of TdT-positive T-cells, despite being a non-neoplastic disease, underscoring the significance of distinguishing it from T-cell acute lymphoblastic leukemia (T-ALL). i-TLP is expected to gain wider recognition and further advancements in understanding its pathology. Here, we present the case of a 59-year-old woman with T-ALL characterized by cycles of progression and SR followed by a rapid blast proliferation. This is the first reported case of T-ALL with repeated SR for more than one year, making this case an extremely rare clinical presentation. This challenging case will enhance comprehension of T-cell tumor pathogenesis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318983","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 : 2024-09-24DOI: 10.1016/j.prp.2024.155605
Parkinson’s Disease (PD) is a chronic and progressive neurodebilitating disorder that affects both motor and non-motor functions. PD is the second most commonly occurring brain disorder after Alzheimer’s disease. The incidence rate of PD was found to be 17 per 100000 per year. The prevalence of the disease is at its peak at age 70 and older. One of the major reasons for the failure to devise a complete therapeutic cure for PD is an inability to identify the exact pathological cause. Recent research has also stated that PD originates in the gut way before the symptoms begin to manifest in an affected person. This might be due to the transmission of pathological alpha-synuclein (α-syn) from the gut to the brain via the vagus nerve. The involvement of toxic environmental exposure in the generation of major disorders like cancer, brain disorders etc, is not an entirely new notion. Our genes are affected directly by the environment. Simultaneously, a number of environmental pollutants may contribute significantly to the trigger of alpha-synuclein misfolding in the brain during PD. In the present review, we will mainly focus on understanding the pathological cascade of PD and how it is triggered by environmental pollutants.
{"title":"Environmental pollutants and alpha-synuclein toxicity in Parkinson’s disease","authors":"","doi":"10.1016/j.prp.2024.155605","DOIUrl":"10.1016/j.prp.2024.155605","url":null,"abstract":"<div><div>Parkinson’s Disease (PD) is a chronic and progressive neurodebilitating disorder that affects both motor and non-motor functions. PD is the second most commonly occurring brain disorder after Alzheimer’s disease. The incidence rate of PD was found to be 17 per 100000 per year. The prevalence of the disease is at its peak at age 70 and older. One of the major reasons for the failure to devise a complete therapeutic cure for PD is an inability to identify the exact pathological cause. Recent research has also stated that PD originates in the gut way before the symptoms begin to manifest in an affected person. This might be due to the transmission of pathological alpha-synuclein (α-syn) from the gut to the brain via the vagus nerve. The involvement of toxic environmental exposure in the generation of major disorders like cancer, brain disorders etc, is not an entirely new notion. Our genes are affected directly by the environment. Simultaneously, a number of environmental pollutants may contribute significantly to the trigger of alpha-synuclein misfolding in the brain during PD. In the present review, we will mainly focus on understanding the pathological cascade of PD and how it is triggered by environmental pollutants.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356696","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 : 2024-09-22DOI: 10.1016/j.prp.2024.155596
Background
Oxaliplatin (OXA) is a vital tool in the chemotherapy of gastric cancer (GC) patients. Circular RNAs (circRNAs) are a group of non-coding RNAs that have been associated with tumorigenesis. Nevertheless, the function of circRNAs in OXA resistance of GC is unknown.
Methods
Circ_0006089/miR-217/NRP1 were elucidated through qRT-PCR in GC OXA-tolerant tissues and cell lines. OXA half-inhibitory concentration (IC50) was quantified by MTT assay. RNA pull-down and luciferase reporter tests were applied to characterize the interaction between circ_0006089 and miR-217, miR-217 and NRP1 in GC cells.
Results
The findings disclosed that circ_0006089 and NRP1 was heightened whereas miR-217 was dramatically declined in OXA-tolerant GC tissues and cell lines. OXA resistance was reduced and the proliferation, migration and invasion ability of OXA cells were diminished after silencing circ_0006089. In addition, circ_0006089 raised OXA resistance by sponging miR-217. Further studies revealed that miR-217 bound to NRP1 and weakened OXA resistance. In addition, it was found that circ_0006089 accelerated GC progression and OXA resistance by upregulating NRP1 expression via sponging miR-217.
Conclusion
Circ_0006089 regulated OXA resistance in GC cells through miR-217/NRP1 axis, implying it was a promising biomarker for GC therapy.
{"title":"circ_0006089 facilitates gastric cancer progression and oxaliplatin resistance via miR-217/NRP1","authors":"","doi":"10.1016/j.prp.2024.155596","DOIUrl":"10.1016/j.prp.2024.155596","url":null,"abstract":"<div><h3>Background</h3><div>Oxaliplatin (OXA) is a vital tool in the chemotherapy of gastric cancer (GC) patients. Circular RNAs (circRNAs) are a group of non-coding RNAs that have been associated with tumorigenesis. Nevertheless, the function of circRNAs in OXA resistance of GC is unknown.</div></div><div><h3>Methods</h3><div>Circ_0006089/miR-217/NRP1 were elucidated through qRT-PCR in GC OXA-tolerant tissues and cell lines. OXA half-inhibitory concentration (IC50) was quantified by MTT assay. RNA pull-down and luciferase reporter tests were applied to characterize the interaction between circ_0006089 and miR-217, miR-217 and NRP1 in GC cells.</div></div><div><h3>Results</h3><div>The findings disclosed that circ_0006089 and NRP1 was heightened whereas miR-217 was dramatically declined in OXA-tolerant GC tissues and cell lines. OXA resistance was reduced and the proliferation, migration and invasion ability of OXA cells were diminished after silencing circ_0006089. In addition, circ_0006089 raised OXA resistance by sponging miR-217. Further studies revealed that miR-217 bound to NRP1 and weakened OXA resistance. In addition, it was found that circ_0006089 accelerated GC progression and OXA resistance by upregulating NRP1 expression via sponging miR-217.</div></div><div><h3>Conclusion</h3><div>Circ_0006089 regulated OXA resistance in GC cells through miR-217/NRP1 axis, implying it was a promising biomarker for GC therapy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315472","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 : 2024-09-22DOI: 10.1016/j.prp.2024.155597
Targeted therapies are often more tolerable than traditional cytotoxic ones. Nurses play a critical role in providing patients and caregivers with information about the disease, available therapies, and the kind, severity, and identification of any potential adverse events. By doing this, it may be possible to ensure that any adverse effects are managed quickly, maximizing the therapeutic benefit. In colorectal cancer (CRC), autophagy-related activities are significantly influenced by miRNAs and exosomal miRNAs. CRC development and treatment resistance have been associated with the cellular process of autophagy. miRNAs, which are short non-coding RNA molecules, have the ability to control the expression of genes by binding to the 3′ untranslated region (UTR) of target mRNAs and either preventing or suppressing translation. It has been discovered that several miRNAs are significant regulators of CRC autophagy. By preventing autophagy, these miRNAs enhance the survival and growth of cancer cells. Exosomes are small membrane vesicles that are released by cells and include miRNAs among other bioactive compounds. Exosomes have the ability to modify recipient cells' biological processes by delivering their cargo, which includes miRNAs. It has been demonstrated that exosomal miRNAs control autophagy in CRC in both autocrine and paracrine ways. We will discuss the potential roles of miRNAs, exosomal miRNAs, and circRNAs in CRC autophagy processes and how nursing care can reduce unfavorable outcomes.
{"title":"Autophagy-related miRNAs, exosomal miRNAs, and circRNAs in tumor progression and drug-and radiation resistance in colorectal cancer","authors":"","doi":"10.1016/j.prp.2024.155597","DOIUrl":"10.1016/j.prp.2024.155597","url":null,"abstract":"<div><div>Targeted therapies are often more tolerable than traditional cytotoxic ones. Nurses play a critical role in providing patients and caregivers with information about the disease, available therapies, and the kind, severity, and identification of any potential adverse events. By doing this, it may be possible to ensure that any adverse effects are managed quickly, maximizing the therapeutic benefit. In colorectal cancer (CRC), autophagy-related activities are significantly influenced by miRNAs and exosomal miRNAs. CRC development and treatment resistance have been associated with the cellular process of autophagy. miRNAs, which are short non-coding RNA molecules, have the ability to control the expression of genes by binding to the 3′ untranslated region (UTR) of target mRNAs and either preventing or suppressing translation. It has been discovered that several miRNAs are significant regulators of CRC autophagy. By preventing autophagy, these miRNAs enhance the survival and growth of cancer cells. Exosomes are small membrane vesicles that are released by cells and include miRNAs among other bioactive compounds. Exosomes have the ability to modify recipient cells' biological processes by delivering their cargo, which includes miRNAs. It has been demonstrated that exosomal miRNAs control autophagy in CRC in both autocrine and paracrine ways. We will discuss the potential roles of miRNAs, exosomal miRNAs, and circRNAs in CRC autophagy processes and how nursing care can reduce unfavorable outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472149","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 : 2024-09-20DOI: 10.1016/j.prp.2024.155573
Background
MicroRNAs act as oncogenes or tumor suppressors in various cancers. The tumor microenvironment (TME) plays an important role in tumor cell progression and survival.
Methods
MicroRNA expressions were evaluated by using NanoString nCounter assay, qRT-PCR and in situ hybridization. Correlation between MircoRNA expressions and TME factors, clinicopathological behaviors and prognostic significance were assessed in 323 surgically resected colorectal cancers.
Results
The microRNA-206 expression was identified significantly higher in Glasgow microenvironment score (GMS) 0 than in GMS 1 or GMS 2 by using the NanoString nCounter assay and qRT-PCR. High microRNA-206 expression was identified in 155 (48.0 %) cases in in situ hybridization and was significantly correlated with low pT classification, and absence of lymphovascular and perineural invasion, and lymph node metastasis. MicroRNA-206 expression was significantly associated with low tumor stroma percentage (TSP), high Klintrup–Mäkinen (KM) grade and low GMS. Patients with high microRNA-206 expression showed significantly better 5-year overall survival than those with low microRNA-206 expression, and was an independent prognostic factor in patients with colorectal cancer. High miR-206 expression was associated with TME, favorable clinicopathologic behaviors and overall survival and presents an independent prognostic factor in patients with colorectal cancer.
Conclusion
Thus, MicroRNA-206 expression presents a feasible prognostic factor and potential therapeutic target to treat patients with colorectal cancer.
{"title":"MicroRNA-206 overexpression is associated with a prominent inflammatory reaction and a favorable colorectal cancer prognosis","authors":"","doi":"10.1016/j.prp.2024.155573","DOIUrl":"10.1016/j.prp.2024.155573","url":null,"abstract":"<div><h3>Background</h3><div>MicroRNAs act as oncogenes or tumor suppressors in various cancers. The tumor microenvironment (TME) plays an important role in tumor cell progression and survival.</div></div><div><h3>Methods</h3><div>MicroRNA expressions were evaluated by using NanoString nCounter assay, qRT-PCR and in situ hybridization. Correlation between MircoRNA expressions and TME factors<strong>,</strong> clinicopathological behaviors and prognostic significance were assessed in 323 surgically resected colorectal cancers.</div></div><div><h3>Results</h3><div>The microRNA-206 expression was identified significantly higher in Glasgow microenvironment score (GMS) 0 than in GMS 1 or GMS 2 by using the NanoString nCounter assay and qRT-PCR. High microRNA-206 expression was identified in 155 (48.0 %) cases in in situ hybridization and was significantly correlated with low pT classification, and absence of lymphovascular and perineural invasion, and lymph node metastasis. MicroRNA-206 expression was significantly associated with low tumor stroma percentage (TSP), high Klintrup–Mäkinen (KM) grade and low GMS. Patients with high microRNA-206 expression showed significantly better 5-year overall survival than those with low microRNA-206 expression, and was an independent prognostic factor in patients with colorectal cancer. High miR-206 expression was associated with TME, favorable clinicopathologic behaviors and overall survival and presents an independent prognostic factor in patients with colorectal cancer.</div></div><div><h3>Conclusion</h3><div>Thus, MicroRNA-206 expression presents a feasible prognostic factor and potential therapeutic target to treat patients with colorectal cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318981","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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