Patients older than the expected age of the local population generally have limited life expectancy. The optimal treatment approach for very elderly patients with head and neck cancer remains uncertain. This study retrospectively analyzed patients over 78 years old, the expected age in 2019 for Chinese individuals, who underwent treatment for head and neck cancer at a tertiary cancer center in China. The study compared the overall survival rates among different treatment groups. The findings revealed that among patients eligible for surgery, radical resection yielded better outcomes compared to radiotherapy-based treatments, with a hazard ratio of 0.362 (95% CI 0.160-0.819, P = 0.015). Among patients who received radiotherapy, those who received a total dose exceeding 60 Gy had a significantly longer survival compared to those who received palliative doses, with median survival time of 31 months versus 14 months (P = 0.003). Among 78 patients who underwent conventional fractionated radiotherapy (CFRT), 15 patients (19.23%) experienced unscheduled treatment breaks with a median duration of 12 days. However, these treatment breaks did not appear to impact survival (P > 0.1). The study also suggested that altered fractionated radiotherapy, including hypofractionated radiotherapy (hypo-RT), could be a viable alternative to CFRT, offering similar survival outcomes with reduced treatment duration. In conclusion, eligible patients should be treated with curative intent, even if they are older than the expected age of the local population. When radiotherapy is indicated, altered fractionation, particularly hypo-RT, may be a favorable option to consider.
{"title":"Treatment outcome of elderly patients (≥ 78 years) with head and neck squamous cell carcinoma: A single center experience.","authors":"Yi Liu, Dan Wang, Yue Deng, Shichuan Zhang","doi":"10.17305/bb.2024.10516","DOIUrl":"10.17305/bb.2024.10516","url":null,"abstract":"<p><p>Patients older than the expected age of the local population generally have limited life expectancy. The optimal treatment approach for very elderly patients with head and neck cancer remains uncertain. This study retrospectively analyzed patients over 78 years old, the expected age in 2019 for Chinese individuals, who underwent treatment for head and neck cancer at a tertiary cancer center in China. The study compared the overall survival rates among different treatment groups. The findings revealed that among patients eligible for surgery, radical resection yielded better outcomes compared to radiotherapy-based treatments, with a hazard ratio of 0.362 (95% CI 0.160-0.819, P = 0.015). Among patients who received radiotherapy, those who received a total dose exceeding 60 Gy had a significantly longer survival compared to those who received palliative doses, with median survival time of 31 months versus 14 months (P = 0.003). Among 78 patients who underwent conventional fractionated radiotherapy (CFRT), 15 patients (19.23%) experienced unscheduled treatment breaks with a median duration of 12 days. However, these treatment breaks did not appear to impact survival (P > 0.1). The study also suggested that altered fractionated radiotherapy, including hypofractionated radiotherapy (hypo-RT), could be a viable alternative to CFRT, offering similar survival outcomes with reduced treatment duration. In conclusion, eligible patients should be treated with curative intent, even if they are older than the expected age of the local population. When radiotherapy is indicated, altered fractionation, particularly hypo-RT, may be a favorable option to consider.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Electrical storms (ESs) following percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) patients pose a significant challenge, affecting prognostic outcomes and increasing mortality. This meta-analysis synthesized data from 11 studies involving 9,666 AMI patients to identify risk factors associated with ES following PCI. Our findings revealed an average ES incidence of 7.70%, with identified risk factors including low thrombolysis in myocardial infarction (TIMI) flow grades (0-1), elevated cardiac troponin I levels, persistent hypotension, reperfusion arrhythmias, the right coronary artery being the infarct-related artery, increased diameter of the infarct-related artery, renal dysfunction, elevated creatine kinase-MB, and bradycardia. Notably, the use of β-blockers was found to significantly reduce the risk of ES. The study underscores the importance of early identification and management of these risk factors in AMI patients undergoing PCI to prevent the occurrence of ES, highlighting the protective role of β-blockers. This research provides a foundation for future strategies aimed at reducing the incidence and improving the prognosis of ES in this patient population.
急性心肌梗死(AMI)患者经皮冠状动脉介入治疗(PCI)后发生电风暴(ES)是一项重大挑战,会影响预后结果并增加死亡率。这项荟萃分析综合了 11 项研究的数据,涉及 9,666 名急性心肌梗死患者,以确定与 PCI 后发生电击相关的风险因素。我们的研究结果显示,ES 的平均发生率为 7.70%,已确定的风险因素包括心肌梗死溶栓(TIMI)血流分级低(0-1 级)、心肌肌钙蛋白 I 水平升高、持续低血压、再灌注心律失常、右冠状动脉为梗死相关动脉、梗死相关动脉直径增大、肾功能不全、肌酸激酶-MB 升高和心动过缓。值得注意的是,使用β-受体阻滞剂可显著降低ES风险。该研究强调了在接受 PCI 治疗的 AMI 患者中早期识别和管理这些风险因素对预防 ES 发生的重要性,并突出了 β 受体阻滞剂的保护作用。这项研究为未来旨在降低这类患者 ES 发生率和改善 ES 预后的策略奠定了基础。
{"title":"Risk factors for electrical storms following percutaneous coronary intervention in patients with acute myocardial infarction: A meta-analysis.","authors":"Xiao Xiong, Qiang Ye, Yongquan Peng","doi":"10.17305/bb.2024.10274","DOIUrl":"10.17305/bb.2024.10274","url":null,"abstract":"<p><p>Electrical storms (ESs) following percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) patients pose a significant challenge, affecting prognostic outcomes and increasing mortality. This meta-analysis synthesized data from 11 studies involving 9,666 AMI patients to identify risk factors associated with ES following PCI. Our findings revealed an average ES incidence of 7.70%, with identified risk factors including low thrombolysis in myocardial infarction (TIMI) flow grades (0-1), elevated cardiac troponin I levels, persistent hypotension, reperfusion arrhythmias, the right coronary artery being the infarct-related artery, increased diameter of the infarct-related artery, renal dysfunction, elevated creatine kinase-MB, and bradycardia. Notably, the use of β-blockers was found to significantly reduce the risk of ES. The study underscores the importance of early identification and management of these risk factors in AMI patients undergoing PCI to prevent the occurrence of ES, highlighting the protective role of β-blockers. This research provides a foundation for future strategies aimed at reducing the incidence and improving the prognosis of ES in this patient population.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease that can be clinically and radiologically mistaken for carcinoma. Although its etiology remains uncertain, potential associations with pregnancy, lactation, hormonal imbalances, autoimmunity, smoking, and various microorganisms have been suggested. This study aimed to evaluate the relationship between IGM and oral health. We included 42 female patients diagnosed with IGM based on histopathological evaluations conducted between September 2018 and October 2023. The reference group consisted of 47 female patients with clinically, radiologically, and laboratory-proven non-specific mastitis and 36 healthy female individuals. The oral health of all participants was evaluated by an experienced dentist using the "Decayed, Missing and Filled Teeth" (DMFT) index and the "Simplified Oral Hygiene Index" (OHI-S). The ages of IGM patients included in this study ranged from 29 to 51 years, with a mean age of 34.88 ± 4.87 years. The most common clinical findings were pain (n = 38), palpable breast mass, erythema, induration, and dermal sinus. Comparison of the OHI-S and DMFT index values among participants revealed that those diagnosed with IGM had significantly higher values than those in the reference group (P < 0.05). Our findings suggest a potential involvement of poor oral health in the etiology of IGM. Future studies should consider oral health as a factor in IGM etiology and explore the oral microbiota in samples obtained from the affected tissue.
{"title":"Is poor oral health a risk factor for idiopathic granulomatous mastitis?","authors":"Semih Sağlık, Enver Ay, Şilan Bilek Olgaç, Necip Nas, Bilal Altunışık","doi":"10.17305/bb.2024.10324","DOIUrl":"10.17305/bb.2024.10324","url":null,"abstract":"<p><p>Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease that can be clinically and radiologically mistaken for carcinoma. Although its etiology remains uncertain, potential associations with pregnancy, lactation, hormonal imbalances, autoimmunity, smoking, and various microorganisms have been suggested. This study aimed to evaluate the relationship between IGM and oral health. We included 42 female patients diagnosed with IGM based on histopathological evaluations conducted between September 2018 and October 2023. The reference group consisted of 47 female patients with clinically, radiologically, and laboratory-proven non-specific mastitis and 36 healthy female individuals. The oral health of all participants was evaluated by an experienced dentist using the \"Decayed, Missing and Filled Teeth\" (DMFT) index and the \"Simplified Oral Hygiene Index\" (OHI-S). The ages of IGM patients included in this study ranged from 29 to 51 years, with a mean age of 34.88 ± 4.87 years. The most common clinical findings were pain (n = 38), palpable breast mass, erythema, induration, and dermal sinus. Comparison of the OHI-S and DMFT index values among participants revealed that those diagnosed with IGM had significantly higher values than those in the reference group (P < 0.05). Our findings suggest a potential involvement of poor oral health in the etiology of IGM. Future studies should consider oral health as a factor in IGM etiology and explore the oral microbiota in samples obtained from the affected tissue.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advancements in artificial intelligence (AI) offer promising tools for improving diagnostic accuracy and patient outcomes in cardiovascular medicine. This study explores the potential of AI-assisted measurements in enhancing the prediction of major adverse cardiac events (MACE) in patients with coronary artery disease (CAD). We conducted a retrospective cohort study involving patients diagnosed with CAD who underwent coronary computed tomography angiography (CCTA). Participants were classified into MACE and non-MACE groups based on their clinical outcomes. Clinical characteristics and AI-assisted measurements of CCTA parameters, including CT-derived fractional flow reserve (CT-FFR) and fat attenuation index (FAI), were collected. Both univariate and multivariable logistic regression analyses were performed to identify independent predictors of MACE, which were used to build predictive models. Statistical analyses revealed three independent predictors of MACE: severe stenosis, CT-FFR ≤ 0.8, and mean FAI (P < 0.05). Seven predictive models incorporating various combinations of these predictors were developed. The model combining all three predictors demonstrated superior performance, as evidenced by the receiver operating characteristic (ROC) curve, with an area under the curve (AUC) of 0.811 (95% confidence interval [CI] 0.774 - 0.847), a sensitivity of 0.776, and a specificity of 0.726. Our findings suggest that AI-assisted CCTA analysis, particularly using fractional flow reserve (FFR) and FAI, could significantly improve the prediction of MACE in patients with CAD, thereby potentially aiding clinical decision making.
{"title":"Artificial intelligence-assisted measurements of coronary computed tomography angiography parameters such as stenosis, flow reserve, and fat attenuation for predicting major adverse cardiac events in patients with coronary arterial disease.","authors":"Cheng Luo, Liang Mo, Zisan Zeng, Muliang Jiang, Bihong T Chen","doi":"10.17305/bb.2024.10497","DOIUrl":"10.17305/bb.2024.10497","url":null,"abstract":"<p><p>Advancements in artificial intelligence (AI) offer promising tools for improving diagnostic accuracy and patient outcomes in cardiovascular medicine. This study explores the potential of AI-assisted measurements in enhancing the prediction of major adverse cardiac events (MACE) in patients with coronary artery disease (CAD). We conducted a retrospective cohort study involving patients diagnosed with CAD who underwent coronary computed tomography angiography (CCTA). Participants were classified into MACE and non-MACE groups based on their clinical outcomes. Clinical characteristics and AI-assisted measurements of CCTA parameters, including CT-derived fractional flow reserve (CT-FFR) and fat attenuation index (FAI), were collected. Both univariate and multivariable logistic regression analyses were performed to identify independent predictors of MACE, which were used to build predictive models. Statistical analyses revealed three independent predictors of MACE: severe stenosis, CT-FFR ≤ 0.8, and mean FAI (P < 0.05). Seven predictive models incorporating various combinations of these predictors were developed. The model combining all three predictors demonstrated superior performance, as evidenced by the receiver operating characteristic (ROC) curve, with an area under the curve (AUC) of 0.811 (95% confidence interval [CI] 0.774 - 0.847), a sensitivity of 0.776, and a specificity of 0.726. Our findings suggest that AI-assisted CCTA analysis, particularly using fractional flow reserve (FFR) and FAI, could significantly improve the prediction of MACE in patients with CAD, thereby potentially aiding clinical decision making.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A wealth of research indicates that superficial gastritis (SG) and atrophic gastritis (AG) are precursors to gastric cancer (GC). While Helicobacter pylori (H. pylori) has long been recognized as a key player in GC development, recent findings by Fu et al. have identified Streptococcus anginosus (S. anginosus) as an emerging pathogen that can trigger SG, AG and GC. S. anginosus, a gram-positive coccus, leverages its surface protein T. pallidum membrane protein C (TMPC) to engage with the annexin A2 (ANXA2) receptor of gastric epithelial cells, facilitating its colonization and invasion in the gastric mucosa. This leads to an upregulation of proinflammatory chemokines Ccl20 and Ccl8, causing prolonged effects on gastric barrier function and microbiota homeostasis, leading to SG. Moreover, these bacteria activate the mitogen-activated protein kinase (MAPK) signaling pathway, which is associated with the development of AG and GC. Importantly, inhibiting TMPC or knocking down ANXA2 can reduce S. anginosus colonization and invasion, lowering the chances of SG, AG, and GC. This paper highlights the molecular mechanisms of S. anginosus in SG, AG and GC, emphasizing the importance of a multi-pathogen strategy in gastric disease management and the need for further investigation into the role of S. anginosus in GC progression.
{"title":"<i>Streptococcus anginosus</i>: A new pathogen of superficial gastritis, atrophic gastritis and gastric cancer.","authors":"Fengting Guo, Lanfang Li, Lifang Li","doi":"10.17305/bb.2024.10705","DOIUrl":"10.17305/bb.2024.10705","url":null,"abstract":"<p><p>A wealth of research indicates that superficial gastritis (SG) and atrophic gastritis (AG) are precursors to gastric cancer (GC). While Helicobacter pylori (H. pylori) has long been recognized as a key player in GC development, recent findings by Fu et al. have identified Streptococcus anginosus (S. anginosus) as an emerging pathogen that can trigger SG, AG and GC. S. anginosus, a gram-positive coccus, leverages its surface protein T. pallidum membrane protein C (TMPC) to engage with the annexin A2 (ANXA2) receptor of gastric epithelial cells, facilitating its colonization and invasion in the gastric mucosa. This leads to an upregulation of proinflammatory chemokines Ccl20 and Ccl8, causing prolonged effects on gastric barrier function and microbiota homeostasis, leading to SG. Moreover, these bacteria activate the mitogen-activated protein kinase (MAPK) signaling pathway, which is associated with the development of AG and GC. Importantly, inhibiting TMPC or knocking down ANXA2 can reduce S. anginosus colonization and invasion, lowering the chances of SG, AG, and GC. This paper highlights the molecular mechanisms of S. anginosus in SG, AG and GC, emphasizing the importance of a multi-pathogen strategy in gastric disease management and the need for further investigation into the role of S. anginosus in GC progression.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141602292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Studies have shown that the prostaglandin (PG) family acts as an allergic inflammatory mediator in malignant diseases. Furthermore, prostaglandin E2 (PGE2) and its related receptors, as well as the prostaglandin D2 (PGD2)/PGD2 receptor (PTGDR2), play irreplaceable roles in tumorigenesis and anti-tumor therapy. Several experiments have demonstrated that PGD2 signaling through PTGDR2 not only directly inhibits cancer cell survival, proliferation, and migration but also reduces resistance toward conventional chemotherapeutic agents. Recent studies from our and other laboratories have shown that PGD2, its ligands, and related metabolites can significantly alter the tumor microenvironment (TME) by promoting the secretion of chemokines and cytokines, thereby inhibiting tumor progression. Additionally, reduced PGD2 expression has been associated with poor prognosis in patients with gastric, breast, lung, and pancreatic cancers, validating the preclinical findings and their clinical relevance. This review focuses on the current understanding of PGD2/PTGDR2 expression patterns and biological activity in cancer, proposing questions to guide the assessment of PGD2 and its receptors as potential targets for effective cancer therapies.
{"title":"Advances in PGD2/PTGDR2 signaling pathway in tumors: A review.","authors":"Hengjin Tian, Kunpeng Ge, Lulu Wang, Peiyao Gao, Amin Chen, Feifan Wang, Fangzheng Guo, FengChao Wang, Qiang Zhang","doi":"10.17305/bb.2024.10485","DOIUrl":"10.17305/bb.2024.10485","url":null,"abstract":"<p><p>Studies have shown that the prostaglandin (PG) family acts as an allergic inflammatory mediator in malignant diseases. Furthermore, prostaglandin E2 (PGE2) and its related receptors, as well as the prostaglandin D2 (PGD2)/PGD2 receptor (PTGDR2), play irreplaceable roles in tumorigenesis and anti-tumor therapy. Several experiments have demonstrated that PGD2 signaling through PTGDR2 not only directly inhibits cancer cell survival, proliferation, and migration but also reduces resistance toward conventional chemotherapeutic agents. Recent studies from our and other laboratories have shown that PGD2, its ligands, and related metabolites can significantly alter the tumor microenvironment (TME) by promoting the secretion of chemokines and cytokines, thereby inhibiting tumor progression. Additionally, reduced PGD2 expression has been associated with poor prognosis in patients with gastric, breast, lung, and pancreatic cancers, validating the preclinical findings and their clinical relevance. This review focuses on the current understanding of PGD2/PTGDR2 expression patterns and biological activity in cancer, proposing questions to guide the assessment of PGD2 and its receptors as potential targets for effective cancer therapies.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Changchang Lu, Lu Zou, Qiaoli Wang, Mengna Sun, Tianyu Shi, Shuang Xu, Fanyan Meng, Juan Du
Kirsten Rat Sarcoma viral oncogene homolog (KRAS) is one of the most frequent oncogenes. However, there are limited treatment options due to its intracellular expression. To address this, we developed a novel bispecific T-cell engager (BiTE) antibody targeting HLA-A2/KRAS G12V complex and CD3 (HLA-G12V/CD3 BiTE). We examined its specific binding to tumor cells and T cells, as well as its anti-tumor effects in vivo. HLA-G12V/CD3 BiTE was expressed in Escherichia coli and its binding affinities to CD3 and HLA-A2/KRAS G12V were measured by flow cytometry, along with T-cell activation. In a xenograft pancreatic tumor model, the HLA-G12V/CD3 BiTE's anti-tumor effects were assessed through tumor growth, survival time, and safety. Our results demonstrated specific binding of HLA-G12V/CD3 BiTE to tumor cells with an HLA-A2/KRAS G12V mutation and T cells. The HLA-G12V/CD3 BiTE also activated T-cells in the presence of tumor cells in vitro. HLA-G12V/CD3 BiTE in vivo testing showed delayed tumor growth without severe toxicity to major organs and prolonged mouse survival. This study highlights the potential of constructing BiTEs recognizing an HLA-peptide complex and providing a novel therapy for cancer treatment targeting the intracellular tumor antigen.
克氏鼠肉瘤病毒癌基因同源体(KRAS)是最常见的癌基因之一。然而,由于其在细胞内的表达,治疗方案十分有限。为了解决这个问题,我们开发了一种新型双特异性 T 细胞吸引子(BiTE)抗体,靶向 HLA-A2/KRAS G12V 复合物和 CD3(HLA-G12V/CD3 BiTE)。我们研究了它与肿瘤细胞和 T 细胞的特异性结合及其在体内的抗肿瘤效果。我们在大肠杆菌中表达了 HLA-G12V/CD3 BiTE,并通过流式细胞术测量了它与 CD3 和 HLA-A2/KRAS G12V 的结合亲和力以及 T 细胞活化情况。在异种移植胰腺肿瘤模型中,通过肿瘤生长、存活时间和安全性评估了 HLA-G12V/CD3 BiTE 的抗肿瘤效果。我们的研究结果表明,HLA-G12V/CD3 BiTE 能与 HLA-A2/KRAS G12V 突变的肿瘤细胞和 T 细胞特异性结合。在体外,HLA-G12V/CD3 BiTE 还能在肿瘤细胞存在的情况下激活 T 细胞。HLA-G12V/CD3 BiTE 的体内测试表明,它能延缓肿瘤生长,对主要器官无严重毒性,并能延长小鼠存活时间。这项研究强调了构建识别 HLA 肽复合物的 BiTE 的潜力,并为针对细胞内肿瘤抗原的癌症治疗提供了一种新疗法。
{"title":"Potent antitumor activity of a bispecific T-cell engager antibody targeting the intracellular antigen KRAS G12V.","authors":"Changchang Lu, Lu Zou, Qiaoli Wang, Mengna Sun, Tianyu Shi, Shuang Xu, Fanyan Meng, Juan Du","doi":"10.17305/bb.2024.10431","DOIUrl":"10.17305/bb.2024.10431","url":null,"abstract":"<p><p>Kirsten Rat Sarcoma viral oncogene homolog (KRAS) is one of the most frequent oncogenes. However, there are limited treatment options due to its intracellular expression. To address this, we developed a novel bispecific T-cell engager (BiTE) antibody targeting HLA-A2/KRAS G12V complex and CD3 (HLA-G12V/CD3 BiTE). We examined its specific binding to tumor cells and T cells, as well as its anti-tumor effects in vivo. HLA-G12V/CD3 BiTE was expressed in Escherichia coli and its binding affinities to CD3 and HLA-A2/KRAS G12V were measured by flow cytometry, along with T-cell activation. In a xenograft pancreatic tumor model, the HLA-G12V/CD3 BiTE's anti-tumor effects were assessed through tumor growth, survival time, and safety. Our results demonstrated specific binding of HLA-G12V/CD3 BiTE to tumor cells with an HLA-A2/KRAS G12V mutation and T cells. The HLA-G12V/CD3 BiTE also activated T-cells in the presence of tumor cells in vitro. HLA-G12V/CD3 BiTE in vivo testing showed delayed tumor growth without severe toxicity to major organs and prolonged mouse survival. This study highlights the potential of constructing BiTEs recognizing an HLA-peptide complex and providing a novel therapy for cancer treatment targeting the intracellular tumor antigen.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana M Serrano Ardila, Gilda S Garza Mayén, Alejandro Gaviño-Vergara
Dear Editor, We have read the article "The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders", recently published in your esteemed journal. We are a team dedicated to diagnosing, approaching, and managing patients with connective tissue disorders, particularly hypermobile spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS). We appreciate the research group's effort to address the complexity of connective tissue disorders using a multi-panel genetic approach and their analysis of genotype-phenotype associations in a cohort of Mexican patients. However, we would like to express our concern regarding two specific points that we consider crucial for the comprehensive understanding and management of these disorders. Read more in the PDF.
亲爱的编辑,我们阅读了贵刊最近发表的文章 "基因小组在墨西哥马凡综合征和其他结缔组织疾病患者分类和提高诊断准确性中的作用"。我们是一个致力于诊断、治疗和管理结缔组织疾病患者的团队,尤其是高移动性频谱疾病 (HSD) 和埃勒斯-丹洛斯综合征 (EDS)。我们赞赏研究小组利用多面板遗传方法解决结缔组织疾病复杂性的努力,以及他们对墨西哥患者队列中基因型-表型关联的分析。然而,我们希望就两个具体问题表达我们的担忧,我们认为这两个问题对于全面了解和管理这些疾病至关重要。阅读 PDF 中的更多内容。
{"title":"Letter regarding \"The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders\".","authors":"Ana M Serrano Ardila, Gilda S Garza Mayén, Alejandro Gaviño-Vergara","doi":"10.17305/bb.2024.10799","DOIUrl":"10.17305/bb.2024.10799","url":null,"abstract":"<p><p>Dear Editor, We have read the article \"The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders\", recently published in your esteemed journal. We are a team dedicated to diagnosing, approaching, and managing patients with connective tissue disorders, particularly hypermobile spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS). We appreciate the research group's effort to address the complexity of connective tissue disorders using a multi-panel genetic approach and their analysis of genotype-phenotype associations in a cohort of Mexican patients. However, we would like to express our concern regarding two specific points that we consider crucial for the comprehensive understanding and management of these disorders. Read more in the PDF.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ajwan Z Albalawi, Areej S Alatawi, Shekha M Al-Atwi, Lama S Alhwyty, Kadi M Alharbi, Shahad A Alshehri, Wasayf A Almarwani, Khulud K Aljohani, Hanan M Hassan, Mohammed M H Al-Gayyar
Hepatocellular carcinoma (HCC) affects approximately 800,000 individuals globally each year. Despite advancements in HCC treatments, there is still a pressing need to identify new drugs that can combat resistance. One potential option is echinacoside, a natural caffeic acid glycoside with antioxidant, anti-inflammatory, antidepressant, and antidiabetic properties. Therefore, we aimed to investigate the ability of echinacoside to exhibit antitumor activity against HCC in rats through ameliorating hepatic fibrosis and tumor invasion. Rats were given thioacetamide to induce HCC, and some were given 30 mg/kg of echinacoside twice a week for 16 weeks. The liver impairment was assessed by measuring serum α-fetoprotein (AFP) and examining liver sections stained with Masson trichrome or anti-transforming growth factor (TGF)-β1 antibodies. The hepatic expression of mRNA and protein levels of TGF-β1, β-catenin, SMAD4, matrix metalloproteinase-9 (MMP9), phosphoinositide 3-kinases (PI3K), mammalian target of rapamycin (mTOR), connective tissue growth factor 2 (CCN2), E-Cadherin, platelets derived growth factor (PDGF)-B and fascin were also analyzed. Echinacoside improved the survival rate of rats by decreasing serum AFP and the number of hepatic nodules. Examination of micro-images indicated that echinacoside can reduce fibrosis. It also significantly decreased the expression of TGF-β1, β-catenin, SMAD4, MMP9, PI3K, mTOR, CCN2, PDGF-B, and fascin while enhancing the expression of E-Cadherin. In conclusion, echinacoside exhibits a protective effect against HCC by increasing survival rates and decreasing tumor growth. It also acts as an inhibitor of the hepatic tissue fibrosis pathway by reducing the expression of TGF-β1, β-catenin, SMAD4, PI3K, CCN2, PDGF-B and mTOR. Additionally, it prevents tumor invasion by suppressing MMP9 and fascin, and increasing the expression of E-Cadherin.
{"title":"Echinacoside ameliorates hepatic fibrosis and tumor invasion in rats with thioacetamide-induced hepatocellular carcinoma.","authors":"Ajwan Z Albalawi, Areej S Alatawi, Shekha M Al-Atwi, Lama S Alhwyty, Kadi M Alharbi, Shahad A Alshehri, Wasayf A Almarwani, Khulud K Aljohani, Hanan M Hassan, Mohammed M H Al-Gayyar","doi":"10.17305/bb.2024.10367","DOIUrl":"10.17305/bb.2024.10367","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) affects approximately 800,000 individuals globally each year. Despite advancements in HCC treatments, there is still a pressing need to identify new drugs that can combat resistance. One potential option is echinacoside, a natural caffeic acid glycoside with antioxidant, anti-inflammatory, antidepressant, and antidiabetic properties. Therefore, we aimed to investigate the ability of echinacoside to exhibit antitumor activity against HCC in rats through ameliorating hepatic fibrosis and tumor invasion. Rats were given thioacetamide to induce HCC, and some were given 30 mg/kg of echinacoside twice a week for 16 weeks. The liver impairment was assessed by measuring serum α-fetoprotein (AFP) and examining liver sections stained with Masson trichrome or anti-transforming growth factor (TGF)-β1 antibodies. The hepatic expression of mRNA and protein levels of TGF-β1, β-catenin, SMAD4, matrix metalloproteinase-9 (MMP9), phosphoinositide 3-kinases (PI3K), mammalian target of rapamycin (mTOR), connective tissue growth factor 2 (CCN2), E-Cadherin, platelets derived growth factor (PDGF)-B and fascin were also analyzed. Echinacoside improved the survival rate of rats by decreasing serum AFP and the number of hepatic nodules. Examination of micro-images indicated that echinacoside can reduce fibrosis. It also significantly decreased the expression of TGF-β1, β-catenin, SMAD4, MMP9, PI3K, mTOR, CCN2, PDGF-B, and fascin while enhancing the expression of E-Cadherin. In conclusion, echinacoside exhibits a protective effect against HCC by increasing survival rates and decreasing tumor growth. It also acts as an inhibitor of the hepatic tissue fibrosis pathway by reducing the expression of TGF-β1, β-catenin, SMAD4, PI3K, CCN2, PDGF-B and mTOR. Additionally, it prevents tumor invasion by suppressing MMP9 and fascin, and increasing the expression of E-Cadherin.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nermin Salkić, Mirela Bašić Denjagić, Nađa Zubčević, Renata Tamburić, Azra Husić Selimović, Emil Babić, Milenko Bevanda, Aida Saray, Predrag Jovanović, Zoran Tošić, Aleksandar Dobrovoljski, Tatjana Barać
Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), necessitates effective management strategies. This study aims to evaluate the real-world efficacy of vedolizumab, a newer biological therapy, in treating IBD in Bosnia and Herzegovina. A retrospective observational study was conducted across six medical centers, involving 139 IBD patients, 76 with UC and 63 with CD. Patients were assessed for clinical remission and other outcomes at the 26-week mark post vedolizumab treatment initiation. At 26 weeks, clinical remission was achieved in 82.9% of UC patients and 85.7% of CD patients. Mucosal healing was observed in 38.1% of CD patients. The efficacy of vedolizumab did not significantly differ based on prior anti-tumor necrosis factor (anti-TNF) exposure. Notably, the clinical scoring tools for predicting vedolizumab response showed limited applicability in this cohort. Vedolizumab demonstrated high efficacy in treating both UC and CD in real-world settings in Bosnia and Herzegovina, underscoring its potential as a significant therapeutic option in IBD management.
{"title":"Short-term efficacy of vedolizumab in patients with inflammatory bowel disease in real-life settings in Bosnia and Herzegovina.","authors":"Nermin Salkić, Mirela Bašić Denjagić, Nađa Zubčević, Renata Tamburić, Azra Husić Selimović, Emil Babić, Milenko Bevanda, Aida Saray, Predrag Jovanović, Zoran Tošić, Aleksandar Dobrovoljski, Tatjana Barać","doi":"10.17305/bb.2024.10433","DOIUrl":"10.17305/bb.2024.10433","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), necessitates effective management strategies. This study aims to evaluate the real-world efficacy of vedolizumab, a newer biological therapy, in treating IBD in Bosnia and Herzegovina. A retrospective observational study was conducted across six medical centers, involving 139 IBD patients, 76 with UC and 63 with CD. Patients were assessed for clinical remission and other outcomes at the 26-week mark post vedolizumab treatment initiation. At 26 weeks, clinical remission was achieved in 82.9% of UC patients and 85.7% of CD patients. Mucosal healing was observed in 38.1% of CD patients. The efficacy of vedolizumab did not significantly differ based on prior anti-tumor necrosis factor (anti-TNF) exposure. Notably, the clinical scoring tools for predicting vedolizumab response showed limited applicability in this cohort. Vedolizumab demonstrated high efficacy in treating both UC and CD in real-world settings in Bosnia and Herzegovina, underscoring its potential as a significant therapeutic option in IBD management.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}