Background/aim: The usefulness of robotic surgery compared to laparoscopic surgery for rectal cancer has been reported; however, few reports exist on robotic abdominoperineal resection (APR). The aim of this study was to compare the outcomes of robotic and laparoscopic surgery to determine their usefulness in patients with locally advanced rectal cancer who had undergone preoperative chemoradiotherapy (CRT).
Patients and methods: This retrospective study included 43 patients with locally advanced rectal cancer who underwent preoperative CRT and robotic (22 patients) or laparoscopic APR (21 patients) between December 2012 and September 2022. We examined the short- and long-term outcomes in the robotic and laparoscopic groups.
Results: The median follow-up durations were 36 and 48 months for the robotic and laparoscopic groups, respectively. No significant differences in operative time, intraoperative blood loss, or overall complication rates were observed. However, the incidence of organ/space surgical site infection (SSI) was significantly lower in the robotic surgery group than in the laparoscopic group (9.1% vs. 38.1%, p=0.034) and the 3-year overall survival rate was significantly higher in the robotic surgery group than in the laparoscopic group (95% vs. 67%, p=0.029).
Conclusion: Robotic APR was associated with a significantly lower rate of organ/space SSIs than the laparoscopic approach, indicating the usefulness of the robotic approach.
背景/目的:有报道称,与腹腔镜手术相比,机器人手术对直肠癌很有用;但关于机器人腹腔镜切除术(APR)的报道很少。本研究的目的是比较机器人手术和腹腔镜手术的疗效,以确定它们对术前接受过放化疗(CRT)的局部晚期直肠癌患者是否有用:这项回顾性研究纳入了43例局部晚期直肠癌患者,他们在2012年12月至2022年9月期间接受了术前CRT和机器人(22例)或腹腔镜APR(21例)手术。我们研究了机器人组和腹腔镜组的短期和长期疗效:机器人组和腹腔镜组的中位随访时间分别为36个月和48个月。手术时间、术中失血量和总体并发症发生率无明显差异。然而,机器人手术组器官/空间手术部位感染(SSI)的发生率明显低于腹腔镜手术组(9.1% vs. 38.1%,P=0.034),机器人手术组的3年总生存率明显高于腹腔镜手术组(95% vs. 67%,P=0.029):结论:与腹腔镜方法相比,机器人APR的器官/间隙SSI发生率明显较低,这表明了机器人方法的实用性。
{"title":"Robotic <i>Versus</i> Laparoscopic Abdominoperineal Resection for Locally Advanced Rectal Cancer Following Preoperative Chemoradiotherapy.","authors":"Tatsuki Watanabe, Kazuhito Sasaki, Hiroaki Nozawa, Koji Murono, Shigenobu Emoto, Hiroyuki Matsuzaki, Yuichiro Yokoyama, Shinya Abe, Yuzo Nagai, Takahide Shinagawa, Hirofumi Sonoda, Lim Sukchol, Soichiro Ishihara","doi":"10.21873/invivo.13636","DOIUrl":"10.21873/invivo.13636","url":null,"abstract":"<p><strong>Background/aim: </strong>The usefulness of robotic surgery compared to laparoscopic surgery for rectal cancer has been reported; however, few reports exist on robotic abdominoperineal resection (APR). The aim of this study was to compare the outcomes of robotic and laparoscopic surgery to determine their usefulness in patients with locally advanced rectal cancer who had undergone preoperative chemoradiotherapy (CRT).</p><p><strong>Patients and methods: </strong>This retrospective study included 43 patients with locally advanced rectal cancer who underwent preoperative CRT and robotic (22 patients) or laparoscopic APR (21 patients) between December 2012 and September 2022. We examined the short- and long-term outcomes in the robotic and laparoscopic groups.</p><p><strong>Results: </strong>The median follow-up durations were 36 and 48 months for the robotic and laparoscopic groups, respectively. No significant differences in operative time, intraoperative blood loss, or overall complication rates were observed. However, the incidence of organ/space surgical site infection (SSI) was significantly lower in the robotic surgery group than in the laparoscopic group (9.1% vs. 38.1%, p=0.034) and the 3-year overall survival rate was significantly higher in the robotic surgery group than in the laparoscopic group (95% vs. 67%, p=0.029).</p><p><strong>Conclusion: </strong>Robotic APR was associated with a significantly lower rate of organ/space SSIs than the laparoscopic approach, indicating the usefulness of the robotic approach.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467693","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}
Qiong Wang, Junzhao Duan, Jian Hong, Kexin Ding, Fumin Tai, Jie Zhu, Hanjiang Fu, Xiaofei Zheng, Changhui Ge
Background/aim: The small intestine is one of the organs most vulnerable to ionizing radiation (IR) damage. However, methods to protect against IR-induced intestinal injury are limited. CBLB502, a Toll-like receptor 5 (TLR5) agonist from Salmonella flagellin, exerts radioprotective effects on various tissues and organs. However, the molecular mechanisms by which CBLB502 protects against IR-induced intestinal injury remain unclear. Thus, this study aimed to elucidate the mechanisms underlying IR-induced intestinal injury and the protective effects of CBLB502 against this condition in mice.
Materials and methods: Mice were administered 0.2 mg/kg CBLB502 before IR at different doses for different time points, and then the survival rate, body weight, hemogram, and histopathology of the mice were analyzed.
Results: CBLB502 reduced IR-induced intestinal injury. RNA-seq analysis revealed that different doses and durations of IR induced different regulatory patterns. CBLB502 protected against intestinal injury mainly after IR by reversing the expression of IR-induced genes and regulating immune processes and metabolic pathways.
Conclusion: This study preliminarily describes the regulatory mechanism of IR-induced intestinal injury and the potential molecular protective mechanism of CBLB502, providing a basis for identifying the functional genes and molecular mechanisms that mediate protection against IR-induced injury.
背景/目的:小肠是最容易受到电离辐射(IR)损伤的器官之一。然而,防止 IR 引起的肠道损伤的方法却很有限。CBLB502是一种来自沙门氏菌鞭毛蛋白的Toll样受体5(TLR5)激动剂,可对多种组织和器官产生辐射保护作用。然而,CBLB502 保护红外诱导的肠道损伤的分子机制仍不清楚。因此,本研究旨在阐明红外诱导小鼠肠道损伤的机制以及 CBLB502 对这种情况的保护作用:结果:CBLB502可减少IR诱导的肠道损伤:结果:CBLB502减轻了IR引起的肠道损伤。RNA-seq分析显示,不同剂量和持续时间的红外诱导了不同的调控模式。CBLB502主要通过逆转IR诱导的基因表达、调节免疫过程和代谢途径来保护IR后的肠道损伤:本研究初步描述了IR诱导肠道损伤的调控机制和CBLB502潜在的分子保护机制,为确定IR诱导损伤的功能基因和分子机制提供了依据。
{"title":"Toll-like Receptor Agonist CBLB502 Protects Against Radiation-induced Intestinal Injury in Mice.","authors":"Qiong Wang, Junzhao Duan, Jian Hong, Kexin Ding, Fumin Tai, Jie Zhu, Hanjiang Fu, Xiaofei Zheng, Changhui Ge","doi":"10.21873/invivo.13613","DOIUrl":"10.21873/invivo.13613","url":null,"abstract":"<p><strong>Background/aim: </strong>The small intestine is one of the organs most vulnerable to ionizing radiation (IR) damage. However, methods to protect against IR-induced intestinal injury are limited. CBLB502, a Toll-like receptor 5 (TLR5) agonist from Salmonella flagellin, exerts radioprotective effects on various tissues and organs. However, the molecular mechanisms by which CBLB502 protects against IR-induced intestinal injury remain unclear. Thus, this study aimed to elucidate the mechanisms underlying IR-induced intestinal injury and the protective effects of CBLB502 against this condition in mice.</p><p><strong>Materials and methods: </strong>Mice were administered 0.2 mg/kg CBLB502 before IR at different doses for different time points, and then the survival rate, body weight, hemogram, and histopathology of the mice were analyzed.</p><p><strong>Results: </strong>CBLB502 reduced IR-induced intestinal injury. RNA-seq analysis revealed that different doses and durations of IR induced different regulatory patterns. CBLB502 protected against intestinal injury mainly after IR by reversing the expression of IR-induced genes and regulating immune processes and metabolic pathways.</p><p><strong>Conclusion: </strong>This study preliminarily describes the regulatory mechanism of IR-induced intestinal injury and the potential molecular protective mechanism of CBLB502, providing a basis for identifying the functional genes and molecular mechanisms that mediate protection against IR-induced injury.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467700","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}
Background/aim: Hyperthermia represents an adjuvant local anticancer strategy which relies on the increase of temperature beyond the physiological level. In this study, we investigated the anticancer potential of Fe3O4 and Fe3O4core Aushell nanoparticles as hyperthermic agents in terms of cytotoxicity and studied the expression of cellular markers of proliferation (changes in mRNA levels via real-time polymerase chain reaction).
Materials and methods: The human breast cancer cell line SK-BR-1 was incubated with either Fe3O4 or Fe3O4core Aushell nanoparticles stabilized with tryptophan, prior to hyperthermia treatment. The normal HEK293 cell line was used as a control. Toxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay to estimate possible toxic effects of the tested nanoparticles. After RNA extraction and cDNA synthesis, mRNA expression of three indicators of proliferation, namely marker of proliferation Ki-67, DNA topoisomerase II alpha (TOP2A) and TPX2 microtubule nucleation factor (TPX2), was investigated.
Results: At each concentration tested, Fe3O4core Aushell nanoparticles showed greater toxicity compared to Fe3O4, while SK-BR-3 cells were more susceptible to their cytotoxic effects compared to the HEK293 cell line. The expression of Ki-67, TOP2A and TPX2 was reduced in SK-BR-3 cells by both Fe3O4 or Fe3O4core Aushell nanoparticles compared to untreated cells, while the only observed change in HEK293 cells was the up-regulation of TOP2A.
Conclusion: Both Fe3O4core Aushell and Fe3O4 NPs exhibit increased cytotoxicity to the cancer cell line tested (SK-BR-3) compared to HEK293 cells. The down-regulation in SK-BR-3 cells of the three proliferative markers studied, Ki-67, TOP2A and TPX2, after incubation with NPs suggests that cells that survived thermal destruction were not actively proliferating.
{"title":"Fe<sub>3</sub>O<sub>4</sub> and Fe<sub>3</sub>O<sub>4core</sub> Au<sub>shell</sub>-based Hyperthermia Reduces Expression of Proliferation Markers <i>Ki-67, TOP2A</i> and <i>TPX2</i> in a Human Breast Cancer Cell Line.","authors":"Stamatiki Grammatikaki, Vanessa-Meletia Bala, Hector Katifelis, Dimitra Ioanna Lampropoulou, Iuliia Mukha, Nadiia Vityuk, Nefeli Lagopati, Vassilios Kouloulias, Gerasimos Aravantinos, Maria Gazouli","doi":"10.21873/invivo.13616","DOIUrl":"10.21873/invivo.13616","url":null,"abstract":"<p><strong>Background/aim: </strong>Hyperthermia represents an adjuvant local anticancer strategy which relies on the increase of temperature beyond the physiological level. In this study, we investigated the anticancer potential of Fe<sub>3</sub>O<sub>4</sub> and Fe<sub>3</sub>O<sub>4core</sub> Au<sub>shell</sub> nanoparticles as hyperthermic agents in terms of cytotoxicity and studied the expression of cellular markers of proliferation (changes in mRNA levels via real-time polymerase chain reaction).</p><p><strong>Materials and methods: </strong>The human breast cancer cell line SK-BR-1 was incubated with either Fe<sub>3</sub>O<sub>4</sub> or Fe<sub>3</sub>O<sub>4core</sub> Au<sub>shell</sub> nanoparticles stabilized with tryptophan, prior to hyperthermia treatment. The normal HEK293 cell line was used as a control. Toxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay to estimate possible toxic effects of the tested nanoparticles. After RNA extraction and cDNA synthesis, mRNA expression of three indicators of proliferation, namely marker of proliferation Ki-67, DNA topoisomerase II alpha (TOP2A) and TPX2 microtubule nucleation factor (TPX2), was investigated.</p><p><strong>Results: </strong>At each concentration tested, Fe<sub>3</sub>O<sub>4core</sub> Au<sub>shell</sub> nanoparticles showed greater toxicity compared to Fe<sub>3</sub>O<sub>4</sub>, while SK-BR-3 cells were more susceptible to their cytotoxic effects compared to the HEK293 cell line. The expression of Ki-67, TOP2A and TPX2 was reduced in SK-BR-3 cells by both Fe<sub>3</sub>O<sub>4</sub> or Fe<sub>3</sub>O<sub>4core</sub> Au<sub>shell</sub> nanoparticles compared to untreated cells, while the only observed change in HEK293 cells was the up-regulation of TOP2A.</p><p><strong>Conclusion: </strong>Both Fe<sub>3</sub>O<sub>4core</sub> Au<sub>shell</sub> and Fe<sub>3</sub>O<sub>4</sub> NPs exhibit increased cytotoxicity to the cancer cell line tested (SK-BR-3) compared to HEK293 cells. The down-regulation in SK-BR-3 cells of the three proliferative markers studied, Ki-67, TOP2A and TPX2, after incubation with NPs suggests that cells that survived thermal destruction were not actively proliferating.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467686","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}
Konstantinos Agiannitopoulos, Anastasia Katseli, Kevisa Potska, Christina Ntogka, Georgios N Tsaousis, Nikolaos Tsoulos, Katerina Kampoli, Anastasios Ntavatzikos, Eirini Papadopoulou, George Nasioulas, Anna Koumarianou
Background/aim: Gliomas are highly heterogeneous malignancies originating from diverse cell types within the brain. Although their precise etiology is frequently unknown, risk factors, such as chemical exposure, radiation, and specific uncommon genetic disorders have been identified. Diagnosis typically entails imaging tests, such as magnetic resonance imaging and computed tomography, complemented by a biopsy for confirmation, which may be further validated through genetic testing.
Case report: Next-generation sequencing technology revealed germline co-deletion deletion of cyclin-dependent kinase inhibitor 2 A and B genes (CDKN2A and CDKN2B) in a patient diagnosed with pleomorphic xanthoastrocytoma based on the tumor's molecular characteristics. Following this result, we performed focused genetic analysis with use of multiplex ligation-dependent probe amplification technology for the mother that revealed the same co-deletion. Moreover, due to the father's neuroendocrine pancreatic cancer, application of the NGS technology detected a pathogenic variant in the BRCA1-interacting helicase 1 (BRIP1) gene. Comprehensive multi-gene testing conducted within the familial context, marked by a varied spectrum of cancer type, revealed a constellation of genetic predispositions.
Conclusion: This case study underscores the critical importance of molecular testing for tumor characterization and highlights the pivotal role of genetic testing in facilitating early intervention and screening for at-risk family members. Furthermore, the identification of germline co-deletions in cancer lays the foundation for the development of targeted therapeutic strategies aimed at restoring normal cellular regulation and improving patient management.
背景/目的:胶质瘤是一种高度异质性的恶性肿瘤,起源于脑内不同类型的细胞。虽然它们的确切病因往往不明,但已确定了一些风险因素,如化学接触、辐射和特定的不常见遗传疾病。诊断通常需要进行磁共振成像和计算机断层扫描等影像学检查,并辅以活检进行确认,活检结果可通过基因检测进一步验证:下一代测序技术发现,一名患者的细胞周期蛋白依赖性激酶抑制剂 2 A 和 B 基因(CDKN2A 和 CDKN2B)存在种系共缺失,根据肿瘤的分子特征,该患者被诊断为多形性黄细胞瘤。根据这一结果,我们利用多重连接依赖性探针扩增技术对母亲进行了重点基因分析,结果显示存在相同的共缺失。此外,由于父亲患有神经内分泌性胰腺癌,应用 NGS 技术检测到了 BRCA1-interacting helicase 1 (BRIP1) 基因中的致病变异。在以不同癌症类型为特征的家族背景下进行的多基因综合测试揭示了一系列遗传倾向:本病例研究强调了分子检测对肿瘤特征描述的至关重要性,并突出了基因检测在促进早期干预和筛查高危家庭成员方面的关键作用。此外,癌症种系共缺失的鉴定还为开发旨在恢复正常细胞调节和改善患者管理的靶向治疗策略奠定了基础。
{"title":"Germline Co-deletion of <i>CDKN2A</i> and <i>CDKN2B</i> Genes in Pleomorphic Xanthoastrocytoma: Case Report.","authors":"Konstantinos Agiannitopoulos, Anastasia Katseli, Kevisa Potska, Christina Ntogka, Georgios N Tsaousis, Nikolaos Tsoulos, Katerina Kampoli, Anastasios Ntavatzikos, Eirini Papadopoulou, George Nasioulas, Anna Koumarianou","doi":"10.21873/invivo.13617","DOIUrl":"10.21873/invivo.13617","url":null,"abstract":"<p><strong>Background/aim: </strong>Gliomas are highly heterogeneous malignancies originating from diverse cell types within the brain. Although their precise etiology is frequently unknown, risk factors, such as chemical exposure, radiation, and specific uncommon genetic disorders have been identified. Diagnosis typically entails imaging tests, such as magnetic resonance imaging and computed tomography, complemented by a biopsy for confirmation, which may be further validated through genetic testing.</p><p><strong>Case report: </strong>Next-generation sequencing technology revealed germline co-deletion deletion of cyclin-dependent kinase inhibitor 2 A and B genes (CDKN2A and CDKN2B) in a patient diagnosed with pleomorphic xanthoastrocytoma based on the tumor's molecular characteristics. Following this result, we performed focused genetic analysis with use of multiplex ligation-dependent probe amplification technology for the mother that revealed the same co-deletion. Moreover, due to the father's neuroendocrine pancreatic cancer, application of the NGS technology detected a pathogenic variant in the BRCA1-interacting helicase 1 (BRIP1) gene. Comprehensive multi-gene testing conducted within the familial context, marked by a varied spectrum of cancer type, revealed a constellation of genetic predispositions.</p><p><strong>Conclusion: </strong>This case study underscores the critical importance of molecular testing for tumor characterization and highlights the pivotal role of genetic testing in facilitating early intervention and screening for at-risk family members. Furthermore, the identification of germline co-deletions in cancer lays the foundation for the development of targeted therapeutic strategies aimed at restoring normal cellular regulation and improving patient management.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467636","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}
Background/aim: The activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway has been implicated in canine soft tissue sarcoma (STS) and may serve as a prognostic marker. This study investigated the correlation between PI3K/Akt activation in tumor cells and tumor-infiltrating lymphocytes (TILs).
Materials and methods: A total of 59 STS samples were labeled via immunohistochemistry to calculate the density of TILs, including CD3+ T cells, CD8+ T cells, CD20+ B cells, and FOXP3+ regulatory T cells.
Results: Forty-eight samples (81.3%) had intra-tumoral TILs with a high density of CD3+ T cells (mean: 283.3 cells/mm2) and CD8+ T cells (mean: 134.8 cells/mm2). Conversely, CD20+ B cells (mean: 73.6 cells/mm2) and FOXP3+ regulatory T cells (mean: 9.2 cells/mm2) were scarce. The abundance of CD3+/CD8+, CD3+/CD20+, and CD8+/CD20+ TILs were highly correlated in multivariate analyses (r=0.895, 0.946, and 0.856, respectively). Nonetheless, TIL density was unrelated to clinicopathological parameters (sex, age, tumor location, breed) and tumor grade. The abundance of CD8+ T cells was positively correlated with the activation of PI3K/Akt, indicating that samples with high levels of phospho-Akt and phospho-S6 tend to have a higher CD8+ T cell density (p=0.0032 and 0.0218, respectively). Furthermore, TIL density was correlated with the Ki-67 index, a tumor proliferation and growth marker. Samples with a high Ki-67 index had a significantly higher abundance of CD3+ T cells, CD8+ T cells, and CD20+ B cells (p=0.0392, 0.0254, 0.0380, respectively).
Conclusion: PI3K/Akt pathway activation may influence the infiltration of CD8+ T cells within the tumor microenvironment in canine STS. Prospective studies involving a higher number of cases are warranted to confirm these findings.
{"title":"The Density of CD8<sup>+</sup> Tumor-infiltrating Lymphocytes Correlated With Akt Activation and Ki-67 Index in Canine Soft Tissue Sarcoma.","authors":"Alfarisa Nururrozi, Kyohei Miyanishi, Masaya Igase, Masashi Sakurai, Yusuke Sakai, Mika Tanabe, Takuya Mizuno","doi":"10.21873/invivo.13620","DOIUrl":"10.21873/invivo.13620","url":null,"abstract":"<p><strong>Background/aim: </strong>The activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway has been implicated in canine soft tissue sarcoma (STS) and may serve as a prognostic marker. This study investigated the correlation between PI3K/Akt activation in tumor cells and tumor-infiltrating lymphocytes (TILs).</p><p><strong>Materials and methods: </strong>A total of 59 STS samples were labeled via immunohistochemistry to calculate the density of TILs, including CD3+ T cells, CD8+ T cells, CD20+ B cells, and FOXP3+ regulatory T cells.</p><p><strong>Results: </strong>Forty-eight samples (81.3%) had intra-tumoral TILs with a high density of CD3+ T cells (mean: 283.3 cells/mm<sup>2</sup>) and CD8+ T cells (mean: 134.8 cells/mm<sup>2</sup>). Conversely, CD20+ B cells (mean: 73.6 cells/mm<sup>2</sup>) and FOXP3+ regulatory T cells (mean: 9.2 cells/mm<sup>2</sup>) were scarce. The abundance of CD3+/CD8+, CD3+/CD20+, and CD8+/CD20+ TILs were highly correlated in multivariate analyses (r=0.895, 0.946, and 0.856, respectively). Nonetheless, TIL density was unrelated to clinicopathological parameters (sex, age, tumor location, breed) and tumor grade. The abundance of CD8+ T cells was positively correlated with the activation of PI3K/Akt, indicating that samples with high levels of phospho-Akt and phospho-S6 tend to have a higher CD8+ T cell density (p=0.0032 and 0.0218, respectively). Furthermore, TIL density was correlated with the Ki-67 index, a tumor proliferation and growth marker. Samples with a high Ki-67 index had a significantly higher abundance of CD3+ T cells, CD8+ T cells, and CD20+ B cells (p=0.0392, 0.0254, 0.0380, respectively).</p><p><strong>Conclusion: </strong>PI3K/Akt pathway activation may influence the infiltration of CD8+ T cells within the tumor microenvironment in canine STS. Prospective studies involving a higher number of cases are warranted to confirm these findings.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467698","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}
Background/aim: Hallux valgus (HV) is the most prevalent deformity affecting the forefoot; however, its genetic etiology remains unclear. In the literature, vitamin D receptor (VDR) genotypes have been reported to be associated with the risk of skeletal malformations accompanied by inflammation. This study aimed to examine the hypothesis that VDR genotypes are associated with the risk of HV.
Materials and methods: The VDR rs731236, rs1544410, rs2228570 and rs7975232 genotypes of 150 HV patients and 600 non-HV subjects were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology and examined regarding their associations with HV risk.
Results: The results showed that none of the genetic frequency distributions of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significant between the HV cases and non-HV controls (p for trend=0.4055, 0.2170, 0.7220, 0.5509, respectively). Additionally, allelic frequency analysis showed that none of the allelic frequencies of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significantly distributed (p=0.2285, 0.1572, 0.9278, and 0.5547, respectively). Furthermore, stratified analysis showed that no correlation was observed between VDR rs731236 and different age groups (either younger or older than 51) or sex (p=0.3953 and p=0.9576). Moreover, no correlation was found between VDR rs731236 genotype and the risk of HV in individuals within subgroups of height, weight, or body mass index (BMI) (p=0.8317, 0.5346, and p=0.8783, respectively).
Conclusion: VDR rs731236, rs1544410, rs2228570, and rs7975232 may not serve as indicators for a higher risk of HV.
{"title":"Impact of Vitamin D Receptor Genotypes on Taiwan Hallux Valgus.","authors":"Chien-Chung Kuo, Chun-Hao Tsai, Tzu-Chieh Lin, Yun-Chi Wang, Hao-Wei Chang, Mei-Chin Mong, Ya-Chen Yang, Wen-Tzu Wu, Shih-Wei Hsu, Wen-Shin Chang, DA-Tian Bau, Chia-Wen Tsai","doi":"10.21873/invivo.13610","DOIUrl":"10.21873/invivo.13610","url":null,"abstract":"<p><strong>Background/aim: </strong>Hallux valgus (HV) is the most prevalent deformity affecting the forefoot; however, its genetic etiology remains unclear. In the literature, vitamin D receptor (VDR) genotypes have been reported to be associated with the risk of skeletal malformations accompanied by inflammation. This study aimed to examine the hypothesis that VDR genotypes are associated with the risk of HV.</p><p><strong>Materials and methods: </strong>The VDR rs731236, rs1544410, rs2228570 and rs7975232 genotypes of 150 HV patients and 600 non-HV subjects were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology and examined regarding their associations with HV risk.</p><p><strong>Results: </strong>The results showed that none of the genetic frequency distributions of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significant between the HV cases and non-HV controls (p for trend=0.4055, 0.2170, 0.7220, 0.5509, respectively). Additionally, allelic frequency analysis showed that none of the allelic frequencies of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significantly distributed (p=0.2285, 0.1572, 0.9278, and 0.5547, respectively). Furthermore, stratified analysis showed that no correlation was observed between VDR rs731236 and different age groups (either younger or older than 51) or sex (p=0.3953 and p=0.9576). Moreover, no correlation was found between VDR rs731236 genotype and the risk of HV in individuals within subgroups of height, weight, or body mass index (BMI) (p=0.8317, 0.5346, and p=0.8783, respectively).</p><p><strong>Conclusion: </strong>VDR rs731236, rs1544410, rs2228570, and rs7975232 may not serve as indicators for a higher risk of HV.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467638","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}
Background/aim: Recent reports indicate that sclerostin is secreted by periodontal ligament tissue-derived (PDL) cells during orthodontic force loading and that the secreted sclerostin contributes to bone metabolism. However, the detailed mechanism is poorly understood. The aim of this study was to determine how PDL cells affect bone formation.
Materials and methods: Rat periodontal ligament tissue was immunohistochemically stained for sclerostin. Cultured primary PDL cells, osteoblasts, and skin fibroblasts (Sfbs) isolated from rat periodontal ligament tissue, calvaria, and skin, respectively, were examined. Osteoblasts were cultured with control conditioned medium (Cont-CDM) and PDL cell culture conditioned medium (PDL-CDM) for up to 21 days. Cultured osteoblasts were then stained with alkaline phosphatase and von Kossa stain. Osteoblasts cultured in each conditioned medium were analyzed by real-time quantitative PCR for bone Gla protein (Bgp), Axin2, and Ki67 expression. PDL cells used to obtain conditioned medium were analyzed for Sost, Ectodin and Wnt1 expression and compared with expression in Sfbs.
Results: Expression of sclerostin was observed in periodontal ligament tissue by immunohistochemical staining. The formation of mineralization nodules was inhibited in PDL-CDM compared with Cont-CDM in osteoblast culture. In PDL-CDM, the expression levels of Bgp and Axin2 in osteoblasts were decreased compared with Cont-CDM. In PDL cells, expression levels of Sost and Ectodin were much higher than in Sfbs; however, expression of Wnt1 was lower in PDL cells compared with Sfbs.
Conclusion: PDL cells secrete various proteins, including sclerostin and suppress osteogenesis in osteoblasts through the canonical Wnt pathway.
{"title":"Effect of Cells Derived from Periodontal Ligament Tissue on Bone Formation.","authors":"Norika Kobayashi, Hiroshi Kadokura, Eisuke Iso, Takako Tsuchiya, Satoshi Yokose","doi":"10.21873/invivo.13609","DOIUrl":"10.21873/invivo.13609","url":null,"abstract":"<p><strong>Background/aim: </strong>Recent reports indicate that sclerostin is secreted by periodontal ligament tissue-derived (PDL) cells during orthodontic force loading and that the secreted sclerostin contributes to bone metabolism. However, the detailed mechanism is poorly understood. The aim of this study was to determine how PDL cells affect bone formation.</p><p><strong>Materials and methods: </strong>Rat periodontal ligament tissue was immunohistochemically stained for sclerostin. Cultured primary PDL cells, osteoblasts, and skin fibroblasts (Sfbs) isolated from rat periodontal ligament tissue, calvaria, and skin, respectively, were examined. Osteoblasts were cultured with control conditioned medium (Cont-CDM) and PDL cell culture conditioned medium (PDL-CDM) for up to 21 days. Cultured osteoblasts were then stained with alkaline phosphatase and von Kossa stain. Osteoblasts cultured in each conditioned medium were analyzed by real-time quantitative PCR for bone Gla protein (Bgp), Axin2, and Ki67 expression. PDL cells used to obtain conditioned medium were analyzed for Sost, Ectodin and Wnt1 expression and compared with expression in Sfbs.</p><p><strong>Results: </strong>Expression of sclerostin was observed in periodontal ligament tissue by immunohistochemical staining. The formation of mineralization nodules was inhibited in PDL-CDM compared with Cont-CDM in osteoblast culture. In PDL-CDM, the expression levels of Bgp and Axin2 in osteoblasts were decreased compared with Cont-CDM. In PDL cells, expression levels of Sost and Ectodin were much higher than in Sfbs; however, expression of Wnt1 was lower in PDL cells compared with Sfbs.</p><p><strong>Conclusion: </strong>PDL cells secrete various proteins, including sclerostin and suppress osteogenesis in osteoblasts through the canonical Wnt pathway.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467631","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}
Background/aim: Distinguishing ovarian metastasis of usual-type endocervical adenocarcinoma (UEA) from primary ovarian tumors is often challenging because of several overlapping features. This study aimed to investigate the clinicopathological characteristics and outcomes of patients with metastatic ovarian UEA.
Patients and methods: Clinicopathological information was collected from eight patients with metastatic ovarian UEA. Immunostaining was also performed.
Results: Most patients presented with adnexal masses that were suspected to be primary ovarian tumors. All examined cases showed block p16 positivity in paired primary and metastatic tumors. Five patients who completed post-operative chemotherapy or concurrent chemoradiotherapy (CCRT) did not experience recurrence. In contrast, one patient who refused further treatment after the first CCRT cycle experienced ovarian and peritoneal metastases. One patient with isolated ovarian metastasis left untreated and developed peritoneal metastasis during follow-up.
Conclusion: Patients with UEA who received proper management for ovarian metastases showed favorable outcomes. Given that ovarian metastatic UEA can mimic primary ovarian borderline tumor or carcinoma of the mucinous or endometrioid type, pathologists should be aware of this unusual but distinctive morphology to avoid misdiagnosis and inappropriate treatment.
{"title":"Ovarian Metastasis from Human Papillomavirus-associated Usual-type Endocervical Adenocarcinoma: Clinicopathological Characteristics for Distinguishing from Primary Ovarian Mucinous or Endometrioid Tumor.","authors":"Yoon Ah Cho, Cheol Keun Park, Hyun-Soo Kim","doi":"10.21873/invivo.13654","DOIUrl":"10.21873/invivo.13654","url":null,"abstract":"<p><strong>Background/aim: </strong>Distinguishing ovarian metastasis of usual-type endocervical adenocarcinoma (UEA) from primary ovarian tumors is often challenging because of several overlapping features. This study aimed to investigate the clinicopathological characteristics and outcomes of patients with metastatic ovarian UEA.</p><p><strong>Patients and methods: </strong>Clinicopathological information was collected from eight patients with metastatic ovarian UEA. Immunostaining was also performed.</p><p><strong>Results: </strong>Most patients presented with adnexal masses that were suspected to be primary ovarian tumors. All examined cases showed block p16 positivity in paired primary and metastatic tumors. Five patients who completed post-operative chemotherapy or concurrent chemoradiotherapy (CCRT) did not experience recurrence. In contrast, one patient who refused further treatment after the first CCRT cycle experienced ovarian and peritoneal metastases. One patient with isolated ovarian metastasis left untreated and developed peritoneal metastasis during follow-up.</p><p><strong>Conclusion: </strong>Patients with UEA who received proper management for ovarian metastases showed favorable outcomes. Given that ovarian metastatic UEA can mimic primary ovarian borderline tumor or carcinoma of the mucinous or endometrioid type, pathologists should be aware of this unusual but distinctive morphology to avoid misdiagnosis and inappropriate treatment.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467659","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}
Background/aim: Reports regarding the association of remdesivir use for the treatment of Coronavirus disease 2019 (COVID-19) with the development of acute kidney injury (AKI) are inconsistent, and the associations between the use of other antivirals and AKI remain unclear. Therefore, this study investigated whether the use of antiviral drugs for the treatment of COVID-19 is a risk factor for the development of AKI.
Patients and methods: This study analyzed 176,197 reports submitted to the Japanese Adverse Event Reporting Database between 2020 and 2022. Reporting odds ratios (RORs) and 95% confidence intervals (95%CIs) for AKI that were associated with the use of antiviral drugs in patients with COVID-19 were calculated after adjusting for potential confounders.
Results: Overall, 5,879 of the reports analyzed were associated with AKI. Signs of AKI were detected with the use of remdesivir [crude ROR (cROR)=2.45; 95%CI=1.91-3.14] and nirmatrelvir/ritonavir (cROR=6.07; 95%CI=4.06-9.06). These results were maintained even after adjusting for potential confounders [remdesivir: adjusted ROR (aROR)=2.18; 95%CI=1.69-2.80, nirmatrelvir/ritonavir: aROR=5.24; 95%CI=3.48-7.90]. However, when analyzing data stratified by reporting year, the association between remdesivir and AKI appeared to diminish over time and was not sustained.
Conclusion: Nirmatrelvir/ritonavir use may be associated with developing AKI. This knowledge may be useful in helping patients with COVID-19 avoid AKI complications.
背景/目的:有关使用雷米替韦治疗冠状病毒病2019(COVID-19)与急性肾损伤(AKI)发生之间的关系的报道并不一致,而使用其他抗病毒药物与AKI之间的关系仍不清楚。因此,本研究调查了使用抗病毒药物治疗COVID-19是否是发生AKI的风险因素:本研究分析了 2020 年至 2022 年期间向日本不良事件报告数据库提交的 176197 份报告。在调整了潜在的混杂因素后,计算了与COVID-19患者使用抗病毒药物相关的AKI报告几率比(ROR)和95%置信区间(95%CI):总体而言,5879 份分析报告与 AKI 相关。使用雷米地韦[粗ROR(cROR)=2.45;95%CI=1.91-3.14]和尼马瑞韦/利托那韦(cROR=6.07;95%CI=4.06-9.06)可检测到AKI迹象。即使调整了潜在的混杂因素[雷米替韦:调整后ROR (aROR)=2.18; 95%CI=1.69-2.80, nirmatrelvir/利托那韦:aROR=5.24; 95%CI=3.48-7.90],这些结果仍然保持不变。然而,当按报告年份对数据进行分层分析时,雷米替韦与AKI之间的关联似乎会随着时间的推移而减弱,并且不会持续:结论:使用奈瑞韦酯/利托那韦可能与发生 AKI 有关。结论:使用尼马瑞韦/利托那韦可能与发生 AKI 有关,这一知识可能有助于帮助 COVID-19 患者避免 AKI 并发症。
{"title":"Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure.","authors":"Masahiro Kamo, Rintaro Sogawa, Chisato Shimanoe","doi":"10.21873/invivo.13637","DOIUrl":"10.21873/invivo.13637","url":null,"abstract":"<p><strong>Background/aim: </strong>Reports regarding the association of remdesivir use for the treatment of Coronavirus disease 2019 (COVID-19) with the development of acute kidney injury (AKI) are inconsistent, and the associations between the use of other antivirals and AKI remain unclear. Therefore, this study investigated whether the use of antiviral drugs for the treatment of COVID-19 is a risk factor for the development of AKI.</p><p><strong>Patients and methods: </strong>This study analyzed 176,197 reports submitted to the Japanese Adverse Event Reporting Database between 2020 and 2022. Reporting odds ratios (RORs) and 95% confidence intervals (95%CIs) for AKI that were associated with the use of antiviral drugs in patients with COVID-19 were calculated after adjusting for potential confounders.</p><p><strong>Results: </strong>Overall, 5,879 of the reports analyzed were associated with AKI. Signs of AKI were detected with the use of remdesivir [crude ROR (cROR)=2.45; 95%CI=1.91-3.14] and nirmatrelvir/ritonavir (cROR=6.07; 95%CI=4.06-9.06). These results were maintained even after adjusting for potential confounders [remdesivir: adjusted ROR (aROR)=2.18; 95%CI=1.69-2.80, nirmatrelvir/ritonavir: aROR=5.24; 95%CI=3.48-7.90]. However, when analyzing data stratified by reporting year, the association between remdesivir and AKI appeared to diminish over time and was not sustained.</p><p><strong>Conclusion: </strong>Nirmatrelvir/ritonavir use may be associated with developing AKI. This knowledge may be useful in helping patients with COVID-19 avoid AKI complications.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467667","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}
Andreas Nitsch, Pauline Marthaler, Sara Qarqash, Maximilian Bemmann, Sander Bekeschus, Georgi I Wassilew, Lyubomir Haralambiev
Background/aim: Cold physical plasma (CPP) has emerged as an effective therapy in oncology by inducing cytotoxic effects in various cancer cells, including chondrosarcoma (CS), Ewing's sarcoma (ES), and osteosarcoma (OS). The current study investigated the impact of CPP on cell motility in CS (CAL-78), ES (A673), and OS (U2-OS) cell lines, focusing on the actin cytoskeleton.
Materials and methods: The CASY Cell Counter and Analyzer was used to study cell proliferation and determine the optimal concentrations of fetal calf serum to maintain viability without stimulation of cell proliferation. CellTiter-BlueCell viability assay was used to determine the effects of CPP on the viability of bone sarcoma cells. The Radius assay was used to determine cell migration. Staining for Deoxyribonuclease I, G-actin, and F-actin was used to assay for the effects on the cytoskeleton.
Results: Reductions in cell viability and motility were observed across all cell lines following CPP treatment. CPP induced changes in the actin cytoskeleton, leading to decreased cell motility.
Conclusion: CPP effectively reduces the motility of bone sarcoma cells by altering the actin cytoskeleton. These findings underscore CPP's potential as a therapeutic tool for bone sarcomas and highlight the need for further research in this area.
{"title":"Cold Physical Plasma Reduces Motility of Various Bone Sarcoma Cells While Remodeling the Cytoskeleton.","authors":"Andreas Nitsch, Pauline Marthaler, Sara Qarqash, Maximilian Bemmann, Sander Bekeschus, Georgi I Wassilew, Lyubomir Haralambiev","doi":"10.21873/invivo.13607","DOIUrl":"10.21873/invivo.13607","url":null,"abstract":"<p><strong>Background/aim: </strong>Cold physical plasma (CPP) has emerged as an effective therapy in oncology by inducing cytotoxic effects in various cancer cells, including chondrosarcoma (CS), Ewing's sarcoma (ES), and osteosarcoma (OS). The current study investigated the impact of CPP on cell motility in CS (CAL-78), ES (A673), and OS (U2-OS) cell lines, focusing on the actin cytoskeleton.</p><p><strong>Materials and methods: </strong>The CASY Cell Counter and Analyzer was used to study cell proliferation and determine the optimal concentrations of fetal calf serum to maintain viability without stimulation of cell proliferation. CellTiter-BlueCell viability assay was used to determine the effects of CPP on the viability of bone sarcoma cells. The Radius assay was used to determine cell migration. Staining for Deoxyribonuclease I, G-actin, and F-actin was used to assay for the effects on the cytoskeleton.</p><p><strong>Results: </strong>Reductions in cell viability and motility were observed across all cell lines following CPP treatment. CPP induced changes in the actin cytoskeleton, leading to decreased cell motility.</p><p><strong>Conclusion: </strong>CPP effectively reduces the motility of bone sarcoma cells by altering the actin cytoskeleton. These findings underscore CPP's potential as a therapeutic tool for bone sarcomas and highlight the need for further research in this area.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467674","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}