Thickening of the ligamentum flavum is the main factor in the development of lumbar spinal canal stenosis (LSCS). Although previous studies have reported factors related to ligamentum flavum thickening, its etiology has not been clarified. Furthermore, it is often difficult to set proper controls to investigate the pathologies of thickening due to differences in patient characteristics, such as age, sex, obesity, and comorbidities. This study aimed to elucidate the pathologies of ligamentum flavum thickening by comparing the dural and dorsal sides of the thickened ligamentum flavum in patients with LSCS. Ligamentum flavum samples were collected from 19 patients with LSCS. The samples were divided into the dural and dorsal sides. The dural side was used as a control to assess the pathologies occurring on the dorsal side. Elastic Masson staining was used to assess the elastic fibres. Gene expression levels were comprehensively assessed using quantitative reverse transcription polymerase chain reaction and DNA microarray analyses. Gene ontology analysis was used to identify biological processes associated with differentially expressed genes. The elastic fibres were significantly decreased on the dorsal side of the thickened ligamentum flavum. Genes related to fibrosis, inflammation, tissue repair, remodeling, and chondrometaplasia, such as COL1A2, COL3A1, COL5A1, TGFB1, VEGFA, TNFA, MMP2, COL10A1, and ADAMTS4, were highly expressed on the dorsal side of the thickened ligamentum flavum. The biological processes occurring on the dorsal side of the thickened ligamentum flavum were extracellular matrix organization, cell adhesion, extracellular matrix disassembly, and proteolysis.These are considered important pathologies of ligamentum flavum thickening.
黄韧带增厚是导致腰椎管狭窄症(LSCS)的主要因素。尽管之前的研究已经报道了黄韧带增厚的相关因素,但其病因尚未明确。此外,由于患者的年龄、性别、肥胖程度和合并症等特征不同,通常很难设置适当的对照来研究增厚的病理。本研究旨在通过比较 LSCS 患者增厚黄韧带的硬膜侧和背侧,阐明黄韧带增厚的病理变化。研究人员从19名LSCS患者身上采集了黄韧带样本。样本分为硬膜侧和背侧。硬膜侧作为对照,以评估背侧发生的病变。弹性马森染色法用于评估弹性纤维。使用定量反转录聚合酶链反应和 DNA 微阵列分析全面评估基因表达水平。基因本体分析用于确定与差异表达基因相关的生物学过程。在增厚的黄韧带背侧,弹性纤维明显减少。与纤维化、炎症、组织修复、重塑和软骨增生相关的基因,如 COL1A2、COL3A1、COL5A1、TGFB1、VEGFA、TNFA、MMP2、COL10A1 和 ADAMTS4 在增厚的黄韧带背侧高表达。黄韧带增厚背侧发生的生物过程包括细胞外基质组织、细胞粘附、细胞外基质分解和蛋白水解。
{"title":"Comparative Gene-Expression Analysis of the Ligamentum Flavum of Patients with Lumbar Spinal Canal Stenosis: Comparison between the Dural and Dorsal Sides of the Thickened Ligamentum Flavum.","authors":"Yutaka Yabe, Taro Takemura, Shinya Hattori, Keisuke Ishikawa, Toshimi Aizawa","doi":"10.1620/tjem.2024.J015","DOIUrl":"10.1620/tjem.2024.J015","url":null,"abstract":"<p><p>Thickening of the ligamentum flavum is the main factor in the development of lumbar spinal canal stenosis (LSCS). Although previous studies have reported factors related to ligamentum flavum thickening, its etiology has not been clarified. Furthermore, it is often difficult to set proper controls to investigate the pathologies of thickening due to differences in patient characteristics, such as age, sex, obesity, and comorbidities. This study aimed to elucidate the pathologies of ligamentum flavum thickening by comparing the dural and dorsal sides of the thickened ligamentum flavum in patients with LSCS. Ligamentum flavum samples were collected from 19 patients with LSCS. The samples were divided into the dural and dorsal sides. The dural side was used as a control to assess the pathologies occurring on the dorsal side. Elastic Masson staining was used to assess the elastic fibres. Gene expression levels were comprehensively assessed using quantitative reverse transcription polymerase chain reaction and DNA microarray analyses. Gene ontology analysis was used to identify biological processes associated with differentially expressed genes. The elastic fibres were significantly decreased on the dorsal side of the thickened ligamentum flavum. Genes related to fibrosis, inflammation, tissue repair, remodeling, and chondrometaplasia, such as COL1A2, COL3A1, COL5A1, TGFB1, VEGFA, TNFA, MMP2, COL10A1, and ADAMTS4, were highly expressed on the dorsal side of the thickened ligamentum flavum. The biological processes occurring on the dorsal side of the thickened ligamentum flavum were extracellular matrix organization, cell adhesion, extracellular matrix disassembly, and proteolysis.These are considered important pathologies of ligamentum flavum thickening.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736254","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}
Recent advancements in computed tomography (CT) scanning have improved the detection rates of peripheral pulmonary nodules, including those with ground-glass opacities (GGOs). This study focuses on part-solid pure ground-glass nodules (GGNs) and aims to identify imaging predictors that can reliably differentiate primary lung cancer from nodules with other diagnoses among part-solid GGNs on high-resolution CT (HRCT). A retrospective study was conducted on 609 patients who underwent surgical treatment or observation for lung nodules. Radiological findings from pre-operative HRCT scans were reviewed and several CT imaging features of part-solid GGNs were examined for their positive predictive value to identify primary lung cancer. The proportions of the nodules with a final diagnosis of primary lung cancer were significantly higher in part-solid GGNs (91.9%) compared with solid nodules (70.3%) or pure GGNs (66.7%). Among CT imaging features of part-solid GGNs that were evaluated, consolidation-to-tumor ratio (CTR) < 0.5 (98.1%), pleural indentation (96.4%), and clear tumor border (96.7%) had high positive predictive value to identify primary lung cancer. When two imaging features were combined, the combination of CTR < 0.5 and a clear tumor border was identified to have 100% positive predictive values with a sensitivity of 40.8%. Thus we conclude that part-solid GGNs with a CTR < 0.5 accompanied by a clear tumor border evaluated by HRCT are very likely to be primary lung cancers with an acceptable sensitivity. Preoperative diagnostic procedures to obtain a pathological diagnosis may potentially be omitted in patients harboring such part-solid GGNs.
{"title":"Morphological Predictors of Primary Lung Cancer among Part-Solid Ground-Grass Nodules on High-Resolution CT.","authors":"Hirotsugu Notsuda, Hiroki Oshio, Ken Onodera, Takashi Hirama, Yui Watanabe, Tatsuaki Watanabe, Takaya Suzuki, Hisashi Oishi, Hiromichi Niikawa, Ryoko Saito-Koyama, Masafumi Noda, Junya Tominaga, Yoshinori Okada","doi":"10.1620/tjem.2024.J016","DOIUrl":"10.1620/tjem.2024.J016","url":null,"abstract":"<p><p>Recent advancements in computed tomography (CT) scanning have improved the detection rates of peripheral pulmonary nodules, including those with ground-glass opacities (GGOs). This study focuses on part-solid pure ground-glass nodules (GGNs) and aims to identify imaging predictors that can reliably differentiate primary lung cancer from nodules with other diagnoses among part-solid GGNs on high-resolution CT (HRCT). A retrospective study was conducted on 609 patients who underwent surgical treatment or observation for lung nodules. Radiological findings from pre-operative HRCT scans were reviewed and several CT imaging features of part-solid GGNs were examined for their positive predictive value to identify primary lung cancer. The proportions of the nodules with a final diagnosis of primary lung cancer were significantly higher in part-solid GGNs (91.9%) compared with solid nodules (70.3%) or pure GGNs (66.7%). Among CT imaging features of part-solid GGNs that were evaluated, consolidation-to-tumor ratio (CTR) < 0.5 (98.1%), pleural indentation (96.4%), and clear tumor border (96.7%) had high positive predictive value to identify primary lung cancer. When two imaging features were combined, the combination of CTR < 0.5 and a clear tumor border was identified to have 100% positive predictive values with a sensitivity of 40.8%. Thus we conclude that part-solid GGNs with a CTR < 0.5 accompanied by a clear tumor border evaluated by HRCT are very likely to be primary lung cancers with an acceptable sensitivity. Preoperative diagnostic procedures to obtain a pathological diagnosis may potentially be omitted in patients harboring such part-solid GGNs.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736255","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}
Xiaoying Song, Yiping Yang, Jingjing Cui, Jing Sun, Jun Zhang, Lichang Gao, Jianqiang Liu
{"title":"Expression of CD4<sup>+</sup>T Cells in Myeloproliferative Diseases and the Effect of Ruxolitinib Treatment on Prognosis.","authors":"Xiaoying Song, Yiping Yang, Jingjing Cui, Jing Sun, Jun Zhang, Lichang Gao, Jianqiang Liu","doi":"10.1620/tjem.2024.J029","DOIUrl":"https://doi.org/10.1620/tjem.2024.J029","url":null,"abstract":"","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155512","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 : 2024-05-24Epub Date: 2024-01-12DOI: 10.1620/tjem.2023.J108
Cong-Ying Chen, Hui Ding, Shang-Shang Wang
This study aimed to investigate the effects of a Roy adaptation model (RAM)-based cognitive stimulation therapy (CST) intervention on elderly patients diagnosed with primary non-small cell lung cancer (NSCLC) undergoing curative resection. A total of 280 patients diagnosed with primary NSCLC were randomized into RAM-based CST group and control group. Outcomes were assessed at three intervals: pre-surgery, discharge, and one-month post-discharge. Cognitive function was evaluated using Mini-Cognitive test. Postoperative delirium prevalence was determined within 48 hours post-surgery using Nursing Delirium Screening Scale. The Hospital Anxiety and Depression Scale evaluated anxiety and depression symptoms, while Quality of Life (QoL) was assessed via Short Form-36 (SF36) Health Survey. The RAM-based CST group demonstrated significantly higher Mini-Cog test scores than the control group upon discharge and post-intervention. Patients with RAM-based CST exhibited a decrease in postoperative delirium compared to the control group. The RAM-based CST intervention yielded an improvement in anxiety and depression at discharge and 1-month post-discharge compared to preoperative levels. Additionally, the RAM-based CST group exhibited substantial enhancements in SF36 subcategory scores at 1-month post-discharge compared to pre-surgery. At post-intervention, the RAM-based CST group demonstrated significantly higher scores than the control group across various health-related domains, including role limitations due to emotional problems, mental health, general health perception, bodily pain, and role limitations due to physical problems. The RAM-based CST intervention in elderly NSCLC patients undergoing curative resection yielded significant enhancements in cognitive function, reduced delirium incidence, improved emotional well-being, and better QoL postoperatively.
{"title":"Effectiveness of Roy Adaptation Model-Based Cognitive Stimulation Therapy in Elderly Patients with Non-Small Cell Lung Cancer Undergoing Curative Resection.","authors":"Cong-Ying Chen, Hui Ding, Shang-Shang Wang","doi":"10.1620/tjem.2023.J108","DOIUrl":"10.1620/tjem.2023.J108","url":null,"abstract":"<p><p>This study aimed to investigate the effects of a Roy adaptation model (RAM)-based cognitive stimulation therapy (CST) intervention on elderly patients diagnosed with primary non-small cell lung cancer (NSCLC) undergoing curative resection. A total of 280 patients diagnosed with primary NSCLC were randomized into RAM-based CST group and control group. Outcomes were assessed at three intervals: pre-surgery, discharge, and one-month post-discharge. Cognitive function was evaluated using Mini-Cognitive test. Postoperative delirium prevalence was determined within 48 hours post-surgery using Nursing Delirium Screening Scale. The Hospital Anxiety and Depression Scale evaluated anxiety and depression symptoms, while Quality of Life (QoL) was assessed via Short Form-36 (SF36) Health Survey. The RAM-based CST group demonstrated significantly higher Mini-Cog test scores than the control group upon discharge and post-intervention. Patients with RAM-based CST exhibited a decrease in postoperative delirium compared to the control group. The RAM-based CST intervention yielded an improvement in anxiety and depression at discharge and 1-month post-discharge compared to preoperative levels. Additionally, the RAM-based CST group exhibited substantial enhancements in SF36 subcategory scores at 1-month post-discharge compared to pre-surgery. At post-intervention, the RAM-based CST group demonstrated significantly higher scores than the control group across various health-related domains, including role limitations due to emotional problems, mental health, general health perception, bodily pain, and role limitations due to physical problems. The RAM-based CST intervention in elderly NSCLC patients undergoing curative resection yielded significant enhancements in cognitive function, reduced delirium incidence, improved emotional well-being, and better QoL postoperatively.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466694","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}
Non-islet cell tumor hypoglycemia (NICTH) is one of the paraneoplastic syndromes manifesting severe hypoglycemia caused by aberrant production of high-molecular-weight insulin-like growth factor 2 (big-IGF2). Two surgical cases of extremely large thoracic solitary fibrous tumors (SFT) with unusual history of NICTH are presented. One case manifested severe hypoglycemia after four years of the first complete surgical resection of the tumor with potential malignant transformation, and the other case showed severe hypoglycemia after ten years of the first detection of the tumor. Meticulous laboratory testing, including serum endocrinological tests and western immunoblotting before and after surgery was performed, and both cases were diagnosed as NICTH. Both patients underwent open thoracic surgery. The patients showed normal glucose and hormone levels immediately after the resection of responsible tumors with elevated blood insulin concentration. SFTs are generally considered benign; however, life-threatening hypoglycemia can happen regardless of treatment. Careful follow-up of the tumor growth is warranted.
{"title":"Evolution of Pleural Solitary Fibrous Tumors Causing Severe Hypoglycemia after Exceptionally Long Asymptomatic Periods: Report of Two Surgical Cases.","authors":"Takaya Suzuki, Hirotsugu Notsuda, Hisashi Oishi, Hiromichi Niikawa, Tatsuaki Watanabe, Yui Watanabe, Ken Onodera, Tetsuto Takeda, Ringo Sugawara, Masafumi Noda, Kanako Sakurai, Mototsugu Nagao, Izumi Fukuda, Yoshinori Okada","doi":"10.1620/tjem.2024.J012","DOIUrl":"10.1620/tjem.2024.J012","url":null,"abstract":"<p><p>Non-islet cell tumor hypoglycemia (NICTH) is one of the paraneoplastic syndromes manifesting severe hypoglycemia caused by aberrant production of high-molecular-weight insulin-like growth factor 2 (big-IGF2). Two surgical cases of extremely large thoracic solitary fibrous tumors (SFT) with unusual history of NICTH are presented. One case manifested severe hypoglycemia after four years of the first complete surgical resection of the tumor with potential malignant transformation, and the other case showed severe hypoglycemia after ten years of the first detection of the tumor. Meticulous laboratory testing, including serum endocrinological tests and western immunoblotting before and after surgery was performed, and both cases were diagnosed as NICTH. Both patients underwent open thoracic surgery. The patients showed normal glucose and hormone levels immediately after the resection of responsible tumors with elevated blood insulin concentration. SFTs are generally considered benign; however, life-threatening hypoglycemia can happen regardless of treatment. Careful follow-up of the tumor growth is warranted.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703520","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}
The aim of this study was to determine the impact of nerve preservation confirmed by intraoperative electrical stimulation (IES) on subjective symptoms of urinary and sexual function in uterine cervical cancer patients who underwent radical hysterectomies. This study included 85 patients who underwent type C radical hysterectomy with IES. Pelvic splanchnic nerve preservation with IES after hysterectomy (nerve-stimulation positive group) was confirmed in 61 women and 24 women did not have nerve preservation (negative group). Urinary function was assessed with the Overactive Bladder Symptom Score (OABSS), International Prostate Symptom Score (IPSS), and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) questionnaires. Sexual function was surveyed using the Female Sexual Function Index (FSFI). Longitudinal changes in those scores according to response to nerve-stimulation were evaluated using a generalized estimating equation. IPSS quality of life (QOL) scores were significantly better in the nerve-stimulation positive group compared with the scores in the negative group until 12 months after surgery, whereas OABSS, IPSS total, IPSS voiding, and ICIQ-SF scores evaluating urinary symptoms were not significantly different between the two groups. FSFI scores were better in the nerve-stimulation positive group 36 months after surgery compared with the scores in the negative group. In this study, we assessed self-reported urinary and sexual symptoms after nerve-sparing radical hysterectomy (NSRH) with IES in the long term. We demonstrated that nerve-sparing significantly reduced distress associated with QOL until 1 year, improved urinary storage symptoms at 2 years, and sexual symptoms 3 years after surgery.
本研究旨在确定通过术中电刺激(IES)确认的神经保留对接受根治性子宫切除术的子宫颈癌患者泌尿和性功能主观症状的影响。本研究纳入了 85 名接受 C 型根治性子宫切除术并接受 IES 的患者。61名妇女在子宫切除术后通过IES保留了盆腔脾神经(神经刺激阳性组),24名妇女没有保留神经(阴性组)。排尿功能通过膀胱过度活动症状评分(OABSS)、国际前列腺症状评分(IPSS)和尿失禁国际咨询问卷短表(ICIQ-SF)进行评估。性功能采用女性性功能指数(FSFI)进行调查。根据对神经刺激的反应来评估这些分数的纵向变化,采用的是广义估计方程。术后12个月前,神经刺激阳性组的IPSS生活质量(QOL)评分明显优于阴性组,而OABSS、IPSS总分、IPSS排尿分和评估排尿症状的ICIQ-SF评分在两组间无明显差异。术后 36 个月后,神经刺激阳性组的 FSFI 评分优于阴性组。在这项研究中,我们评估了神经保留根治性子宫切除术(NSRH)术后自我报告的泌尿和性症状。结果表明,神经保留术后 1 年前,与 QOL 相关的痛苦明显减少,术后 2 年尿储留症状得到改善,术后 3 年性功能症状得到改善。
{"title":"Long-Term and Short-Interval Assessment of Self-Reported Urinary and Sexual Functions after Nerve-Sparing Radical Hysterectomy: A Prospective Cohort Study.","authors":"Masumi Ishibashi, Hitoshi Niikura, Motoko Ishida, Noriyuki Iwama, Hirohito Metoki, Shogo Shigeta, Tomoyuki Nagai, Hideki Tokunaga, Muneaki Shimada, Nobuo Yaegashi","doi":"10.1620/tjem.2024.J014","DOIUrl":"10.1620/tjem.2024.J014","url":null,"abstract":"<p><p>The aim of this study was to determine the impact of nerve preservation confirmed by intraoperative electrical stimulation (IES) on subjective symptoms of urinary and sexual function in uterine cervical cancer patients who underwent radical hysterectomies. This study included 85 patients who underwent type C radical hysterectomy with IES. Pelvic splanchnic nerve preservation with IES after hysterectomy (nerve-stimulation positive group) was confirmed in 61 women and 24 women did not have nerve preservation (negative group). Urinary function was assessed with the Overactive Bladder Symptom Score (OABSS), International Prostate Symptom Score (IPSS), and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) questionnaires. Sexual function was surveyed using the Female Sexual Function Index (FSFI). Longitudinal changes in those scores according to response to nerve-stimulation were evaluated using a generalized estimating equation. IPSS quality of life (QOL) scores were significantly better in the nerve-stimulation positive group compared with the scores in the negative group until 12 months after surgery, whereas OABSS, IPSS total, IPSS voiding, and ICIQ-SF scores evaluating urinary symptoms were not significantly different between the two groups. FSFI scores were better in the nerve-stimulation positive group 36 months after surgery compared with the scores in the negative group. In this study, we assessed self-reported urinary and sexual symptoms after nerve-sparing radical hysterectomy (NSRH) with IES in the long term. We demonstrated that nerve-sparing significantly reduced distress associated with QOL until 1 year, improved urinary storage symptoms at 2 years, and sexual symptoms 3 years after surgery.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703522","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 : 2024-05-01Epub Date: 2024-01-18DOI: 10.1620/tjem.2024.J002
Haoyue Yu, Zhiguo Wang, Yan Dong, Li Li, Xianming Fan, Nan Zheng, Ji Jiang, Caiyu Lin, Conghua Lu, Kunlin Li, Mingxia Feng
Osimertinib, a promising and approved third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is a standard strategy for EGFR-mutant non-small cell lung cancer (NSCLC) patients. However, developed resistance is unavoidable, which reduces its long-term effectiveness. In this study, RNA sequencing was performed to analyze differentially expressed genes (DEGs). The PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to identify the key genes for clinical prognosis and gene correlation respectively. Protein expression was determined by western blot analysis. Cell viability assay and Ki67 staining were used to evaluate the effect of osimertinib on tumor cells. Finally, we screened out two hub genes, myelocytomatosis oncogene (Myc) and axis inhibition protein 1 (Axin1), upregulated in three osimertinib-resistant cell lines through RNA sequencing and bioinformatics analysis. Next, cell experiment confirmed that expression of C-MYC and AXIN1 were elevated in different EGFR mutant NSCLC cell lines with acquired resistance to osimertinib, compared with their corresponding parental cell lines. Furthermore, we demonstrated that AXIN1 upregulated the expression of C-MYC and mediated the acquired resistance of EGFR mutant NSCLC cells to osimertinib in vitro. In conclusion, AXIN1 affected the sensitivity of EGFR mutant NSCLC to osimertinib via regulating C-MYC expression in vitro. Targeting AXIN1/MYC signaling may be a potential new strategy for overcoming acquired resistance to osimertinib.
{"title":"AXIN1/MYC Axis Mediated the Osimertinib Resistance in EGFR Mutant Non-Small Cell Lung Cancer Cells.","authors":"Haoyue Yu, Zhiguo Wang, Yan Dong, Li Li, Xianming Fan, Nan Zheng, Ji Jiang, Caiyu Lin, Conghua Lu, Kunlin Li, Mingxia Feng","doi":"10.1620/tjem.2024.J002","DOIUrl":"10.1620/tjem.2024.J002","url":null,"abstract":"<p><p>Osimertinib, a promising and approved third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is a standard strategy for EGFR-mutant non-small cell lung cancer (NSCLC) patients. However, developed resistance is unavoidable, which reduces its long-term effectiveness. In this study, RNA sequencing was performed to analyze differentially expressed genes (DEGs). The PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to identify the key genes for clinical prognosis and gene correlation respectively. Protein expression was determined by western blot analysis. Cell viability assay and Ki67 staining were used to evaluate the effect of osimertinib on tumor cells. Finally, we screened out two hub genes, myelocytomatosis oncogene (Myc) and axis inhibition protein 1 (Axin1), upregulated in three osimertinib-resistant cell lines through RNA sequencing and bioinformatics analysis. Next, cell experiment confirmed that expression of C-MYC and AXIN1 were elevated in different EGFR mutant NSCLC cell lines with acquired resistance to osimertinib, compared with their corresponding parental cell lines. Furthermore, we demonstrated that AXIN1 upregulated the expression of C-MYC and mediated the acquired resistance of EGFR mutant NSCLC cells to osimertinib in vitro. In conclusion, AXIN1 affected the sensitivity of EGFR mutant NSCLC to osimertinib via regulating C-MYC expression in vitro. Targeting AXIN1/MYC signaling may be a potential new strategy for overcoming acquired resistance to osimertinib.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485876","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}
Anamorelin (ANAM) is a novel ghrelin receptor agonist for the treatment of cancer cachexia. In clinical trials of ANAM, glucose metabolism disorders as adverse effects were relatively frequent, however, when and how they occur remains unclear. Moreover, the safety in patients with pancreatic cancer and/or diabetes has not been clarified because most previous studies focused on patients with non-small cell lung cancer and had excluded patients with poorly controlled diabetes. Herein, a 66-year-old man with advanced pancreatic cancer and diabetes was administered ANAM, and acute hyperglycemia was developed and could be monitored by the self-monitoring of blood glucose (SMBG). Increasing the insulin dose failed to control hyperglycemia adequately, but the hyperglycemia ameliorated quickly after ANAM discontinuation. The continuous glucose monitoring (CGM) revealed that the sensor glucose levels had remained in the high range throughout the day during ANAM administration despite using 1.5 times more insulin. Our report is one of the few that describe the details of ANAM-induced hyperglycemia and provides important information for the safe and effective use of ANAM.
阿那莫瑞林(ANAM)是一种新型胃泌素受体激动剂,用于治疗癌症恶病质。在 ANAM 的临床试验中,作为不良反应的糖代谢紊乱比较常见,但何时以及如何发生仍不清楚。此外,由于之前的研究大多集中在非小细胞肺癌患者身上,并排除了控制不佳的糖尿病患者,因此对胰腺癌和/或糖尿病患者的安全性尚未明确。在本研究中,一名患有晚期胰腺癌和糖尿病的 66 岁男性接受了 ANAM 治疗,并出现了急性高血糖,可通过自我血糖监测(SMBG)进行监测。增加胰岛素剂量未能充分控制高血糖,但在停用 ANAM 后,高血糖迅速缓解。连续血糖监测(CGM)显示,在服用安乃近期间,尽管胰岛素用量增加了 1.5 倍,但传感器的血糖水平全天都保持在较高范围。我们的报告是为数不多的描述 ANAM 引起的高血糖详情的报告之一,为安全有效地使用 ANAM 提供了重要信息。
{"title":"Anamorelin Induced Acute Hyperglycemia in a Patient with Advanced Pancreatic Cancer and Diabetes: A Case Report.","authors":"Junpei Yamamoto, Hiroshi Onodera, Yuki Kaminaga, Yoko Kayaba, Masahiro Usui","doi":"10.1620/tjem.2024.J013","DOIUrl":"10.1620/tjem.2024.J013","url":null,"abstract":"<p><p>Anamorelin (ANAM) is a novel ghrelin receptor agonist for the treatment of cancer cachexia. In clinical trials of ANAM, glucose metabolism disorders as adverse effects were relatively frequent, however, when and how they occur remains unclear. Moreover, the safety in patients with pancreatic cancer and/or diabetes has not been clarified because most previous studies focused on patients with non-small cell lung cancer and had excluded patients with poorly controlled diabetes. Herein, a 66-year-old man with advanced pancreatic cancer and diabetes was administered ANAM, and acute hyperglycemia was developed and could be monitored by the self-monitoring of blood glucose (SMBG). Increasing the insulin dose failed to control hyperglycemia adequately, but the hyperglycemia ameliorated quickly after ANAM discontinuation. The continuous glucose monitoring (CGM) revealed that the sensor glucose levels had remained in the high range throughout the day during ANAM administration despite using 1.5 times more insulin. Our report is one of the few that describe the details of ANAM-induced hyperglycemia and provides important information for the safe and effective use of ANAM.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703519","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}