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Volume 29,Issue 11,2022 Table of Contents
2022, 29(11):971-977.
DOI: 10.3872/j.issn.1007-385X.2022.11.002
Abstract:
In recent years, immune checkpoint inhibitors (ICIs) have made remarkable achievements in the treatment of melanoma.However, the activation of T cells also causes a series of immune-related adverse events (irAEs). Different from traditional chemotherapy, irAEs have a unique manifestation and need unique treatment. Although clinicians gradually attach importance to the incidence and management of irAEs, the mechanism, presentations, diagnosis and monitoring of some irAEs still need to be further summarized to guide clinical practice and clinical trials. However, the mechanism of different irAEs, the influence of steroid therapy, and the risk of patients with autoimmune diseases receiving ICIs are still controversial. This review provided an overview of the presentation, diagnosis, and treatment of irAEs to inspire management strategies and research interests.
In recent years, immune checkpoint inhibitors (ICIs) have made remarkable achievements in the treatment of melanoma.However, the activation of T cells also causes a series of immune-related adverse events (irAEs). Different from traditional chemotherapy, irAEs have a unique manifestation and need unique treatment. Although clinicians gradually attach importance to the incidence and management of irAEs, the mechanism, presentations, diagnosis and monitoring of some irAEs still need to be further summarized to guide clinical practice and clinical trials. However, the mechanism of different irAEs, the influence of steroid therapy, and the risk of patients with autoimmune diseases receiving ICIs are still controversial. This review provided an overview of the presentation, diagnosis, and treatment of irAEs to inspire management strategies and research interests.
2022, 29(11):978-984.
DOI: 10.3872/j.issn.1007-385X.2022.11.003
Abstract:
As a new type of immunotherapy, immune checkpoint inhibitors (ICIs) is another emerging anti-tumor treatment modality after chemotherapy, targeted therapy, and anti-angiogenic therapy, and has brought significant survival benefits to patients with malignant tumors. However, the overall incidence of immune-related adverse events (irAEs) is 79%-82%, and irAEs greatly affect clinical treatment decisions and to some extent limit their clinical application and sustained patient benefit. Almost all organ systems can be affected by irAEs, and their universality, specificity, complexity, and diversity lead to great difficulty in diagnosis and treatment. Adequate recognition and early identification of severe irAEs is particularly important to avoid critical toxicity-related deaths, and therefore critical irAEs require treatment by a multidisciplinary team (MDT). Patients with irAEs of unknown diagnosis, critical condition, poor treatment effect, or whether to restart immunotherapy after toxic remission need standardized and standardized MDT treatment. Therefore, establishing a patient-centered irAEs-MDT model to address critical and difficult irAEs based on evidence-based medicine and guideline consensus will maximize the benefits of immunotherapy for oncology patients.
As a new type of immunotherapy, immune checkpoint inhibitors (ICIs) is another emerging anti-tumor treatment modality after chemotherapy, targeted therapy, and anti-angiogenic therapy, and has brought significant survival benefits to patients with malignant tumors. However, the overall incidence of immune-related adverse events (irAEs) is 79%-82%, and irAEs greatly affect clinical treatment decisions and to some extent limit their clinical application and sustained patient benefit. Almost all organ systems can be affected by irAEs, and their universality, specificity, complexity, and diversity lead to great difficulty in diagnosis and treatment. Adequate recognition and early identification of severe irAEs is particularly important to avoid critical toxicity-related deaths, and therefore critical irAEs require treatment by a multidisciplinary team (MDT). Patients with irAEs of unknown diagnosis, critical condition, poor treatment effect, or whether to restart immunotherapy after toxic remission need standardized and standardized MDT treatment. Therefore, establishing a patient-centered irAEs-MDT model to address critical and difficult irAEs based on evidence-based medicine and guideline consensus will maximize the benefits of immunotherapy for oncology patients.
2022, 29(11):985-988.
DOI: 10.3872/j.issn.1007-385X.2022.11.004
Abstract:
Immunotherapy, based on immune checkpoint inhibitors (ICIs), has become the mainstay of treatment for solid tumors, with broad spectrum and definitive efficacy; however, the subsequent immune-related toxicity, namely immune-related adverse event (irAE), has increasingly become an obstacle to immunotherapy. At present, several guidelines or consensus have provided principled and specific guidance on the diagnosis, classification, treatment, and monitoring of irAE. Considering the management of irAE often involves multiple disciplines, the Chinese Society of Clinical Oncology (CSCO) immunotherapy committee, Antitumor Drug Safety Management Committee organized a panel of clinical experts and published“Chinese Consensus on the Construction of Multidisciplinary Team for Management of Immune Checkpoint Inhibitor-Related Toxicity”.As the author of the consensus, I hereby make a preliminary interpretation of the content of the consensus.
Immunotherapy, based on immune checkpoint inhibitors (ICIs), has become the mainstay of treatment for solid tumors, with broad spectrum and definitive efficacy; however, the subsequent immune-related toxicity, namely immune-related adverse event (irAE), has increasingly become an obstacle to immunotherapy. At present, several guidelines or consensus have provided principled and specific guidance on the diagnosis, classification, treatment, and monitoring of irAE. Considering the management of irAE often involves multiple disciplines, the Chinese Society of Clinical Oncology (CSCO) immunotherapy committee, Antitumor Drug Safety Management Committee organized a panel of clinical experts and published“Chinese Consensus on the Construction of Multidisciplinary Team for Management of Immune Checkpoint Inhibitor-Related Toxicity”.As the author of the consensus, I hereby make a preliminary interpretation of the content of the consensus.
2022, 29(11):989-994.
DOI: 10.3872/j.issn.1007-385X.2022.11.005
Abstract:
免疫检查点抑制剂（ICI）使用的增加导致了免疫相关不良反应（irAE）报告的增加。与传统癌症治疗的不同，这些 irAE 是独特的，通常呈现延迟起病的特点，并且持续时间较长。irAE 可涉及任何器官或系统。irAE 影响通常是低级别的，是可治疗和可逆的；然而，一些副作用可能是严重的，并导致永久性疾病，如免疫性心肌炎、重症肌无力、结肠炎等。治疗主要基于皮质 类固醇和其他免疫调节剂，审慎的irAE 管理对于改善患者生活质量和长期结局至关重要。
免疫检查点抑制剂（ICI）使用的增加导致了免疫相关不良反应（irAE）报告的增加。与传统癌症治疗的不同，这些 irAE 是独特的，通常呈现延迟起病的特点，并且持续时间较长。irAE 可涉及任何器官或系统。irAE 影响通常是低级别的，是可治疗和可逆的；然而，一些副作用可能是严重的，并导致永久性疾病，如免疫性心肌炎、重症肌无力、结肠炎等。治疗主要基于皮质 类固醇和其他免疫调节剂，审慎的irAE 管理对于改善患者生活质量和长期结局至关重要。
2022, 29(11):995-1001.
DOI: 10.3872/j.issn.1007-385X.2022.11.006
Abstract:
Objective: To investigate the clinical characteristics and risk factors of immune-related adverse events (irAEs) and immune checkpoint inhibitor-related pneumonitis (ICI-P) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). Methods: The baseline characteristics, treatment details and data on the occurrence of irAE and ICI-P from general information and clinical characteristics of 114 NSCLC patients who received at least 1 ICI treatment at the Department of Thoracic Oncology, Shanxi Bethune Hospital during January 2019 and December 2021 were retrospectively analyzed. The relationship between patients' clinical characteristics and irAE as well as ICI-P was investigated, and the risk factors for the occurrence of ICI-P were also analyzed. Moreover, the characteristics and treatment outcomes of patients with ICI-P were also observed. Results: There were 68 irAEs occurred in 48 (42.11%) out of 114 NSCLC patients treated with ICIs, with the incidences of overall irAE and severe irAEs of 59.65% and 9.65%, respectively. The organs associated with the incidence of irAE in the descending order (only the top four are listed) were gastrointestinal system >respiratory system >skin > endocrine system; and the ICIs associated with the incidence of irAE were sindilizumab>dulcolizumab>carrelixumab=Pabrolizumab. Age in clinical characteristics was associated with the occurrence of irAE. 15 patients developed ICI-P, with an overall incidence of 13.16%, accounting for 31.25% of all irAE patients, of whom 4 were severe, accounting for 8.33% of the number of irAE and 26.66% of the number of ICI-P. The incidence of ICI-P was higher in patients with combination therapy than those with monotherapy (73.33% vs 26.67%), and the incidence of ICI-P was the highest in patients treated with Sindilizumab (60% of ICI-P cases). A history of smoking was a risk factor for ICI-P. Most of the patients with ICI-P presented with common respiratory symptoms, and all of the severe cases were elderly smokers with severe symptoms and fibrosis or a ground glass appearance on imaging. Only one case did not discontinue ICI, and the rest suspended or delayed ICI and received corticosteroid therapy with good outcomes. Conclusion: The incidence of irAE in ICI-treated NSCLC is high and predominantly in elderly patients. About 1/3 of patients with irAE develop ICI-P and about 1/4 of ICI-P is severe. A history of smoking is a risk factor for the development of ICI-P.
Objective: To investigate the clinical characteristics and risk factors of immune-related adverse events (irAEs) and immune checkpoint inhibitor-related pneumonitis (ICI-P) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). Methods: The baseline characteristics, treatment details and data on the occurrence of irAE and ICI-P from general information and clinical characteristics of 114 NSCLC patients who received at least 1 ICI treatment at the Department of Thoracic Oncology, Shanxi Bethune Hospital during January 2019 and December 2021 were retrospectively analyzed. The relationship between patients' clinical characteristics and irAE as well as ICI-P was investigated, and the risk factors for the occurrence of ICI-P were also analyzed. Moreover, the characteristics and treatment outcomes of patients with ICI-P were also observed. Results: There were 68 irAEs occurred in 48 (42.11%) out of 114 NSCLC patients treated with ICIs, with the incidences of overall irAE and severe irAEs of 59.65% and 9.65%, respectively. The organs associated with the incidence of irAE in the descending order (only the top four are listed) were gastrointestinal system >respiratory system >skin > endocrine system; and the ICIs associated with the incidence of irAE were sindilizumab>dulcolizumab>carrelixumab=Pabrolizumab. Age in clinical characteristics was associated with the occurrence of irAE. 15 patients developed ICI-P, with an overall incidence of 13.16%, accounting for 31.25% of all irAE patients, of whom 4 were severe, accounting for 8.33% of the number of irAE and 26.66% of the number of ICI-P. The incidence of ICI-P was higher in patients with combination therapy than those with monotherapy (73.33% vs 26.67%), and the incidence of ICI-P was the highest in patients treated with Sindilizumab (60% of ICI-P cases). A history of smoking was a risk factor for ICI-P. Most of the patients with ICI-P presented with common respiratory symptoms, and all of the severe cases were elderly smokers with severe symptoms and fibrosis or a ground glass appearance on imaging. Only one case did not discontinue ICI, and the rest suspended or delayed ICI and received corticosteroid therapy with good outcomes. Conclusion: The incidence of irAE in ICI-treated NSCLC is high and predominantly in elderly patients. About 1/3 of patients with irAE develop ICI-P and about 1/4 of ICI-P is severe. A history of smoking is a risk factor for the development of ICI-P.
2022, 29(11):1002-1005.
DOI: 10.3872/j.issn.1007-385X.2022.11.007
Abstract:
免疫检查点抑制剂（ICI）是一种新型抗肿瘤药物，其在产生持久抗肿瘤反应的同时，也可引起多种免疫相关不良反应 （irAE）的发生。irAE 可涉及多个系统，其中眼部irAE 在临床上发生率极低。本文报告2 例恶性黑色素瘤（MM）患者使用ICI 治疗后发生葡萄膜炎。第1 例为青年男性右侧胸壁皮肤MM 患者，予以帕博利珠单抗治疗42 周后，出现双眼结膜充血、畏光、疼痛， 伴视物模糊、变形及视力下降，行眼底荧光素血管造影（FFA）诊断为双眼葡萄膜炎（G3）。第2 例为青年女性直肠MM 患者，予以 特瑞普利单抗治疗12 周后，出现双眼结膜充血、视物模糊和视力下降，行FFA 诊断为双眼葡萄膜炎（G3）。两例患者予以激素治 疗后视力恢复正常或症状得到缓解。ICI 相关眼毒性虽然少见，若不及时发现及治疗会严重影响患者的生活质量，及早诊断和治疗的患者预后较好。
免疫检查点抑制剂（ICI）是一种新型抗肿瘤药物，其在产生持久抗肿瘤反应的同时，也可引起多种免疫相关不良反应 （irAE）的发生。irAE 可涉及多个系统，其中眼部irAE 在临床上发生率极低。本文报告2 例恶性黑色素瘤（MM）患者使用ICI 治疗后发生葡萄膜炎。第1 例为青年男性右侧胸壁皮肤MM 患者，予以帕博利珠单抗治疗42 周后，出现双眼结膜充血、畏光、疼痛， 伴视物模糊、变形及视力下降，行眼底荧光素血管造影（FFA）诊断为双眼葡萄膜炎（G3）。第2 例为青年女性直肠MM 患者，予以 特瑞普利单抗治疗12 周后，出现双眼结膜充血、视物模糊和视力下降，行FFA 诊断为双眼葡萄膜炎（G3）。两例患者予以激素治 疗后视力恢复正常或症状得到缓解。ICI 相关眼毒性虽然少见，若不及时发现及治疗会严重影响患者的生活质量，及早诊断和治疗的患者预后较好。
2022, 29(11):1006-1009.
DOI: 10.3872/j.issn.1007-385X.2022.11.008
Abstract:
随着免疫检查点抑制剂（ICI）在临床越来越广泛的应用，ICI 治疗使肿瘤患者临床获益的同时，也会出现一些免疫相关 不良反应。本文报道了1 例晚期肺鳞癌男性患者使用替雷利珠单抗治疗后致免疫相关性皮肤毒性——史蒂文斯-约翰逊综合征（SJS）/中毒性表皮坏死松解症（TEN），主要表现躯干和四肢皮肤皮疹、红斑、瘙痒、脱皮等，经治疗后好转。通过复习替雷利珠单抗相关不良反应的文献，进一步分析了替雷利珠单抗所致皮肤毒性的临床特点和治疗方法，为提高免疫治疗药物临床应用的安 全性提供了参考。
随着免疫检查点抑制剂（ICI）在临床越来越广泛的应用，ICI 治疗使肿瘤患者临床获益的同时，也会出现一些免疫相关 不良反应。本文报道了1 例晚期肺鳞癌男性患者使用替雷利珠单抗治疗后致免疫相关性皮肤毒性——史蒂文斯-约翰逊综合征（SJS）/中毒性表皮坏死松解症（TEN），主要表现躯干和四肢皮肤皮疹、红斑、瘙痒、脱皮等，经治疗后好转。通过复习替雷利珠单抗相关不良反应的文献，进一步分析了替雷利珠单抗所致皮肤毒性的临床特点和治疗方法，为提高免疫治疗药物临床应用的安 全性提供了参考。
2022, 29(11):1010-1012.
DOI: 10.3872/j.issn.1007-385X.2022.11.009
Abstract:
近年来，免疫检查点抑制剂（ICI）广泛应用于肺癌的治疗中，ICI 引起的不良反应亦逐渐被认识。其中，ICI 相关肝毒性 （IMH）多表现为丙氨酸氨基转移酶及天门冬氨酸氨基转移酶升高，ICI 相关肝硬化性肝毒性报道少见。本文报道1 例本科室收治 的70 岁男性肺鳞状细胞癌（LSCC）病例，该患者应用帕博利珠单抗（200 mg d1 Q3w）维持治疗期间出现腹胀、纳差、乏力、肝功能 异常及肝硬化改变，结合患者病史、症状及检验检查结果诊断为ICI 相关肝硬化性肝毒性，经口服泼尼松（60 mg qd）治疗，患者腹 胀等症状消失、肝功能及肝硬化改变部分好转。通过报道该例ICI 治疗相关不良反应，为临床一线医生处理相关问题时提供了一
近年来，免疫检查点抑制剂（ICI）广泛应用于肺癌的治疗中，ICI 引起的不良反应亦逐渐被认识。其中，ICI 相关肝毒性 （IMH）多表现为丙氨酸氨基转移酶及天门冬氨酸氨基转移酶升高，ICI 相关肝硬化性肝毒性报道少见。本文报道1 例本科室收治 的70 岁男性肺鳞状细胞癌（LSCC）病例，该患者应用帕博利珠单抗（200 mg d1 Q3w）维持治疗期间出现腹胀、纳差、乏力、肝功能 异常及肝硬化改变，结合患者病史、症状及检验检查结果诊断为ICI 相关肝硬化性肝毒性，经口服泼尼松（60 mg qd）治疗，患者腹 胀等症状消失、肝功能及肝硬化改变部分好转。通过报道该例ICI 治疗相关不良反应，为临床一线医生处理相关问题时提供了一
2022, 29(11):1013-1016.
DOI: 10.3872/j.issn.1007-385X.2022.11.010
Abstract:
免疫治疗是目前肿瘤综合治疗体系重要组成部分，免疫检查点抑制剂（ICI）相关性心肌炎（ICI-M）作为免疫相关不良 反应（irAE）的一种，虽然发生率较低，但病死率极高，已引起临床高度关注。本文报道1 例信迪利单抗联合IBI310 治疗恶性黑色 素瘤发生的危重型ICI-M 病例，并复习相关文献，对ICI-M 发病机制、临床表现及诊断治疗等方面的最新进展作一讨论，以期为临床免疫治疗提供有益的资料。
免疫治疗是目前肿瘤综合治疗体系重要组成部分，免疫检查点抑制剂（ICI）相关性心肌炎（ICI-M）作为免疫相关不良 反应（irAE）的一种，虽然发生率较低，但病死率极高，已引起临床高度关注。本文报道1 例信迪利单抗联合IBI310 治疗恶性黑色 素瘤发生的危重型ICI-M 病例，并复习相关文献，对ICI-M 发病机制、临床表现及诊断治疗等方面的最新进展作一讨论，以期为临床免疫治疗提供有益的资料。
2022, 29(11):1017-1020.
DOI: 10.3872/j.issn.1007-385X.2022.11.011
Abstract:
免疫相关性脑炎是一类由机体自身免疫机制介导的脑炎，肿瘤和感染是较明确的诱发因素。免疫检查点抑制剂 （ICI）引起的免疫相关性脑炎鲜有报道。本文报道本院收治的1 例免疫相关性脑炎病例，患者为60 岁男性，因胸膜间皮瘤应用纳 武利尤单抗联合伊匹木单抗治疗，用药后第5 周出现精神行为异常、意识障碍，但脑脊液自身免疫性脑炎相关抗体、副肿瘤综合征相关抗体及寡克隆区带均为阴性，经停止免疫治疗、糖皮质激素大剂量冲击及足量的丙种球蛋白等综合治疗后，患者精神行为及 意识恢复正常，症状好转出院。此外，本文还就免疫相关性脑炎的发病机制、临床表现和诊断治疗等方面进行了相关文献分析讨 论，以期能提高临床医师对免疫相关性脑炎的认识和治疗水平。
免疫相关性脑炎是一类由机体自身免疫机制介导的脑炎，肿瘤和感染是较明确的诱发因素。免疫检查点抑制剂 （ICI）引起的免疫相关性脑炎鲜有报道。本文报道本院收治的1 例免疫相关性脑炎病例，患者为60 岁男性，因胸膜间皮瘤应用纳 武利尤单抗联合伊匹木单抗治疗，用药后第5 周出现精神行为异常、意识障碍，但脑脊液自身免疫性脑炎相关抗体、副肿瘤综合征相关抗体及寡克隆区带均为阴性，经停止免疫治疗、糖皮质激素大剂量冲击及足量的丙种球蛋白等综合治疗后，患者精神行为及 意识恢复正常，症状好转出院。此外，本文还就免疫相关性脑炎的发病机制、临床表现和诊断治疗等方面进行了相关文献分析讨 论，以期能提高临床医师对免疫相关性脑炎的认识和治疗水平。
2022, 29(11):1021-1024.
DOI: 10.3872/j.issn.1007-385X.2022.11.012
Abstract:
恶性黑色素瘤（MM）是一种恶性程度高、早期易转移、死亡率高的肿瘤。随着免疫检查点抑制剂（ICI）为代表的新型 免疫疗法的发展，黑色素瘤患者的总生存期得到了较大提升。然而，在ICI 治疗期间或之后，部分患者可能会出现免疫相关不良 反应（irAE），尤其是在ICI 联合治疗时。免疫相关性肝炎是其常见不良反应，但大多数肝炎病例为轻中度，严重免疫相关性肝炎 的发病率低。报告一例58 岁ⅢC 期肢端恶性黑色素瘤患者，在3 个周期双重免疫治疗后出现了严重免疫相关性肝炎，血检结果提 示总胆红素（TBIL）丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）明显增高，经过大剂量皮质类固醇激素联合吗替麦 考酚酯（MMF）治疗后，患者的TBIL 明显改善，ALT 也恢复正常。
恶性黑色素瘤（MM）是一种恶性程度高、早期易转移、死亡率高的肿瘤。随着免疫检查点抑制剂（ICI）为代表的新型 免疫疗法的发展，黑色素瘤患者的总生存期得到了较大提升。然而，在ICI 治疗期间或之后，部分患者可能会出现免疫相关不良 反应（irAE），尤其是在ICI 联合治疗时。免疫相关性肝炎是其常见不良反应，但大多数肝炎病例为轻中度，严重免疫相关性肝炎 的发病率低。报告一例58 岁ⅢC 期肢端恶性黑色素瘤患者，在3 个周期双重免疫治疗后出现了严重免疫相关性肝炎，血检结果提 示总胆红素（TBIL）丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）明显增高，经过大剂量皮质类固醇激素联合吗替麦 考酚酯（MMF）治疗后，患者的TBIL 明显改善，ALT 也恢复正常。
2022, 29(11):1025-1031.
DOI: 10.3872/j.issn.1007-385X.2022.11.013
Abstract:
Objective: To investigate the effect of transcription factor specificity protein 1 (SP1) knockdown on cisplatin (DDP) resistance in small cell lung cancer (SCLC) H466/DDP cells and its molecular mechanism. Methods: SCLC H466/DDP cells with knockdown of SP1 and simultaneous overexpression of ATP binding cassette subfamily C member 1（ABCC1）were constructed, and the expression of SP1 and ABCC1 in non-drug-resistant and drug-resistant SCLC tissues was detected by IHC method. The correlation between SP1 and ABCC1 expression in SCLC tissues was analyzed by the Spearman r method. Western blot was performed to detect the expression of SP1, ABCC1 and CD44 in transfected H446/DDP cells. The proliferation, apoptosis and self-replication ability of H446/DDP cells were detected by CCK-8, flow cytometry and microsphere assay respectively. Chromatin immunoprecipitation (ChIP) assay was performed to detect whether SP1 is a transcription factor of ABCC1. Results: The protein levels of SP1 and ABCC1 in drug-resistant H446/DDP cells and drug-resistant SCLC tissues were higher than those in parental H446 cells and non-drug-resistant SCLC tissues (all P<0.05), and the expression of SP1 and ABCC1 protein in SCLC tissues was positively correlated. Knockdown of SP1 inhibited the proliferation ability, reduced CD44 and ABCC1 protein expression levels, decreased the number of cell microsphere formation, and promoted apoptosis (all P<0.05) of H446/DDP cells. SP1 was approved to be the transcription factor of ABCC1. Conclusion: Transcription factor SP1 is involved in drug resistance in SCLC H446/DDP cells by regulating ABBC1 expression, and SP1 is a potential therapeutic target for DDP-resistant SCLC.
Objective: To investigate the effect of transcription factor specificity protein 1 (SP1) knockdown on cisplatin (DDP) resistance in small cell lung cancer (SCLC) H466/DDP cells and its molecular mechanism. Methods: SCLC H466/DDP cells with knockdown of SP1 and simultaneous overexpression of ATP binding cassette subfamily C member 1（ABCC1）were constructed, and the expression of SP1 and ABCC1 in non-drug-resistant and drug-resistant SCLC tissues was detected by IHC method. The correlation between SP1 and ABCC1 expression in SCLC tissues was analyzed by the Spearman r method. Western blot was performed to detect the expression of SP1, ABCC1 and CD44 in transfected H446/DDP cells. The proliferation, apoptosis and self-replication ability of H446/DDP cells were detected by CCK-8, flow cytometry and microsphere assay respectively. Chromatin immunoprecipitation (ChIP) assay was performed to detect whether SP1 is a transcription factor of ABCC1. Results: The protein levels of SP1 and ABCC1 in drug-resistant H446/DDP cells and drug-resistant SCLC tissues were higher than those in parental H446 cells and non-drug-resistant SCLC tissues (all P<0.05), and the expression of SP1 and ABCC1 protein in SCLC tissues was positively correlated. Knockdown of SP1 inhibited the proliferation ability, reduced CD44 and ABCC1 protein expression levels, decreased the number of cell microsphere formation, and promoted apoptosis (all P<0.05) of H446/DDP cells. SP1 was approved to be the transcription factor of ABCC1. Conclusion: Transcription factor SP1 is involved in drug resistance in SCLC H446/DDP cells by regulating ABBC1 expression, and SP1 is a potential therapeutic target for DDP-resistant SCLC.
2022, 29(11):1032-1037.
DOI: 10.3872/j.issn.1007-385X.2022.11.014
Abstract:
Objective: To investigate the effect of cystathionine β-synthase (CBS) on the proliferation of lung adenocarcinoma A549 cells through the AKT/cyclin D1 pathway and its molecular mechanism. Methods: Expression of CBS and AKT/cyclinD1-related proteins in lung adenocarcinoma tissues was analyzed by cBioPortal database. The CBS expression in collected lung adenocarcinoma tissues from Chinese patients was verified by immunofluorescence method. WB assay was performed to detect the expression of cysteine metabolism and AKT/cyclin D1 pathway-related proteins in A549 cells and their transplanted tumors, and CBS DNA methylation sequencing was performed to detect the effect of its methylation on CBS mRNA expression in lung cancer cells. The pCW57.1-myrAKT plasmid was co-transfected with RNA interference control plasmid pGIPZ-CBS-nc-shRNA, interference plasmid pGIPZ-CBS-shNRA1 and pGIPZ-CBS-shNRA2, respectively, into A549 cells, which were further sub-divided into DOX+ and DOX-groups. The colony formation ability of A549 cells in each group after transfection was examined by cell colony formation assay. The effect of overexpression of CBS on the growth of transplanted tumors was examined by CBSwt A549 cell- and CBSI278TA549 cell-transplanted tumor assay, and AzMC fluorescence staining and immunohistochemistry were used to detect H2S levels and Ki-67 positivity in transplanted tumor tissues, respectively. Results: Both database analysis and tissue specimens showed that CBS was lowly expressed in lung adenocarcinoma tissues compared with para-cancerous tissues (all P<0.01); CBS protein was lowly expressed in A549, SKMES1 and NCIH460 cells compared with SV-40 cells (all P<0.01), while p-AKT and cyclin D1 protein levels were highly expressed (all P<0.01). Overexpression of AKT in A549 cells significantly promoted the formation of cell colonies (P<0.01), and knockdown of CBS on this basis further promoted the formation of cell colonies (all P<0.01). Transplantation tumor experiments showed that CBS, RB and P21 protein expression was elevated, H2S level was increased, tumor volume was decreased and Ki-67 positivity was reduced in the DOX+ CBSWT group compared with those in the DOX- CBSWT group (all P<0.01); CBS expression was elevated in the DOX+ CBSI278T group compared with the DOX- CBS I278T group (P<0.01), but the changes in H2S level and transplantation tumor volume were not significant. Conclusions: CBS is lowly expressed in lung adenocarcinoma tissues and A549 cells, while the AKT/cyclinD1 pathway is activated. Overexpression or knockdown of CBS can inhibit or promote the growth of A549 cells and their transplanted tumors, and CBS and AKT/cyclin D1 pathway-related proteins may be the potential targets and markers for lung adenocarcinoma.
Objective: To investigate the effect of cystathionine β-synthase (CBS) on the proliferation of lung adenocarcinoma A549 cells through the AKT/cyclin D1 pathway and its molecular mechanism. Methods: Expression of CBS and AKT/cyclinD1-related proteins in lung adenocarcinoma tissues was analyzed by cBioPortal database. The CBS expression in collected lung adenocarcinoma tissues from Chinese patients was verified by immunofluorescence method. WB assay was performed to detect the expression of cysteine metabolism and AKT/cyclin D1 pathway-related proteins in A549 cells and their transplanted tumors, and CBS DNA methylation sequencing was performed to detect the effect of its methylation on CBS mRNA expression in lung cancer cells. The pCW57.1-myrAKT plasmid was co-transfected with RNA interference control plasmid pGIPZ-CBS-nc-shRNA, interference plasmid pGIPZ-CBS-shNRA1 and pGIPZ-CBS-shNRA2, respectively, into A549 cells, which were further sub-divided into DOX+ and DOX-groups. The colony formation ability of A549 cells in each group after transfection was examined by cell colony formation assay. The effect of overexpression of CBS on the growth of transplanted tumors was examined by CBSwt A549 cell- and CBSI278TA549 cell-transplanted tumor assay, and AzMC fluorescence staining and immunohistochemistry were used to detect H2S levels and Ki-67 positivity in transplanted tumor tissues, respectively. Results: Both database analysis and tissue specimens showed that CBS was lowly expressed in lung adenocarcinoma tissues compared with para-cancerous tissues (all P<0.01); CBS protein was lowly expressed in A549, SKMES1 and NCIH460 cells compared with SV-40 cells (all P<0.01), while p-AKT and cyclin D1 protein levels were highly expressed (all P<0.01). Overexpression of AKT in A549 cells significantly promoted the formation of cell colonies (P<0.01), and knockdown of CBS on this basis further promoted the formation of cell colonies (all P<0.01). Transplantation tumor experiments showed that CBS, RB and P21 protein expression was elevated, H2S level was increased, tumor volume was decreased and Ki-67 positivity was reduced in the DOX+ CBSWT group compared with those in the DOX- CBSWT group (all P<0.01); CBS expression was elevated in the DOX+ CBSI278T group compared with the DOX- CBS I278T group (P<0.01), but the changes in H2S level and transplantation tumor volume were not significant. Conclusions: CBS is lowly expressed in lung adenocarcinoma tissues and A549 cells, while the AKT/cyclinD1 pathway is activated. Overexpression or knockdown of CBS can inhibit or promote the growth of A549 cells and their transplanted tumors, and CBS and AKT/cyclin D1 pathway-related proteins may be the potential targets and markers for lung adenocarcinoma.
2022, 29(11):1038-1044.
DOI: 10.3872/j.issn.1007-385X.2022.11.015
Abstract:
Objective: To investigate the expression, function and clinical significance of maternal leucine zipper kinase (MELK) in pancreatic cancer. Methods: The expression of MELK in pancreatic cancer was analyzed and the possible molecular mechanism of MELK in pancreatic cancer was predicted by bioinformatics. The clinical data of 45 patients with pancreatic cancer undergoing surgical treatment in the First Hospital of Lanzhou University were retrospectively analyzed. Immunohistochemistry was used to explore the MELK expression levels in pancreatic cancer tissues and normal para-cancerous tissues, and its relationship with clinical pathological characteristics was also analyzed. The postoperative recurrence time of patients was collected through outpatient records and telephone follow-up to explore the relationship between MELK expression and postoperative recurrence time. Results: MELK mRNA was highly expressed in pancreatic cancer tissues and correlated with the overall survival rate and postoperative recurrence time. Multivariate Cox analysis showed that the MELK gene could be used as an independent prognostic factor in patients with pancreatic cancer. Functional enrichment suggests that MELK is involved in multiple cancer-related functional pathways and is positively correlated with the pathogenic molecules of pancreatic cancer. Immunohistochemistry results showed that MELK in pancreatic cancer tissues was significantly higher than that in adjacent normal tissues. The expression of MELK in pancreatic cancer tissues was correlated with tumor size. Conclusion: The MELK gene is highly expressed in pancreatic cancer tissues and is associated with patients’prognosis. MELK plays a role in the progression of pancreatic cancer and is expected to become a potential biomarker and therapeutic target of pancreatic cancer.
Objective: To investigate the expression, function and clinical significance of maternal leucine zipper kinase (MELK) in pancreatic cancer. Methods: The expression of MELK in pancreatic cancer was analyzed and the possible molecular mechanism of MELK in pancreatic cancer was predicted by bioinformatics. The clinical data of 45 patients with pancreatic cancer undergoing surgical treatment in the First Hospital of Lanzhou University were retrospectively analyzed. Immunohistochemistry was used to explore the MELK expression levels in pancreatic cancer tissues and normal para-cancerous tissues, and its relationship with clinical pathological characteristics was also analyzed. The postoperative recurrence time of patients was collected through outpatient records and telephone follow-up to explore the relationship between MELK expression and postoperative recurrence time. Results: MELK mRNA was highly expressed in pancreatic cancer tissues and correlated with the overall survival rate and postoperative recurrence time. Multivariate Cox analysis showed that the MELK gene could be used as an independent prognostic factor in patients with pancreatic cancer. Functional enrichment suggests that MELK is involved in multiple cancer-related functional pathways and is positively correlated with the pathogenic molecules of pancreatic cancer. Immunohistochemistry results showed that MELK in pancreatic cancer tissues was significantly higher than that in adjacent normal tissues. The expression of MELK in pancreatic cancer tissues was correlated with tumor size. Conclusion: The MELK gene is highly expressed in pancreatic cancer tissues and is associated with patients’prognosis. MELK plays a role in the progression of pancreatic cancer and is expected to become a potential biomarker and therapeutic target of pancreatic cancer.
15 Expression, function and possible mechanism of lncRNA LINC00504 in breast cancer tissues and cells
2022, 29(11):1045-1048.
DOI: 10.3872/j.issn.1007-385X.2022.11.016
Abstract:
目的：探讨lncRNA LINC00504 在乳腺癌中的表达、功能及可能的机制。方法：利用GEPIA 等多个数据库分析 LINC00504 在乳腺癌组织中的表达及其与患者预后关系、与乳腺癌驱动基因相关性，筛选与LINC00504 表达密切相关的关键基 因并分析其相关信号通路。将si-LINC00504 转染三阴性乳腺癌细胞MDA-MB-231 和SKBR3，qPCR 检测转染细胞中LINC00504 的表达；CCK-8 法检测转染细胞的增殖能力。结果：数据库分析显示LINC00504 在乳腺癌组织和体外培养MDA-MB-231 和 SKBR3 细胞中均呈高表达，其高表达患者的PFS 长于低表达患者。LINC00504 表达与乳腺癌驱动基因ERRB2 和BRCA1 呈正相 关、与BRCA2 呈负相关，LINC00504 相关的20 个关键基因涉及多种肿瘤，主要参与氨基酸代谢、糖酵解/糖异生途径。敲减 LINC00504 表达可促进MDA-MB-231 和SKBR3 细胞的增殖。结论：在乳腺癌组织中高表达的LINC00504 与患者PFS 有关联；其相关基因可能参与多种肿瘤的氨基酸和糖代谢；敲减LINC00504 可促进MDA-MB-231 和SKBR3 细胞的增殖。
目的：探讨lncRNA LINC00504 在乳腺癌中的表达、功能及可能的机制。方法：利用GEPIA 等多个数据库分析 LINC00504 在乳腺癌组织中的表达及其与患者预后关系、与乳腺癌驱动基因相关性，筛选与LINC00504 表达密切相关的关键基 因并分析其相关信号通路。将si-LINC00504 转染三阴性乳腺癌细胞MDA-MB-231 和SKBR3，qPCR 检测转染细胞中LINC00504 的表达；CCK-8 法检测转染细胞的增殖能力。结果：数据库分析显示LINC00504 在乳腺癌组织和体外培养MDA-MB-231 和 SKBR3 细胞中均呈高表达，其高表达患者的PFS 长于低表达患者。LINC00504 表达与乳腺癌驱动基因ERRB2 和BRCA1 呈正相 关、与BRCA2 呈负相关，LINC00504 相关的20 个关键基因涉及多种肿瘤，主要参与氨基酸代谢、糖酵解/糖异生途径。敲减 LINC00504 表达可促进MDA-MB-231 和SKBR3 细胞的增殖。结论：在乳腺癌组织中高表达的LINC00504 与患者PFS 有关联；其相关基因可能参与多种肿瘤的氨基酸和糖代谢；敲减LINC00504 可促进MDA-MB-231 和SKBR3 细胞的增殖。
16 Application of tumor-targeting bacteria in the treatment of immunotherapy: from basic to clinical
2022, 29(11):1049-1053.
DOI: 10.3872/j.issn.1007-385X.2022.11.017
Abstract:
目前，肿瘤治疗方法日趋多样，其中细菌治疗渐成近年来的研究热点。细菌治疗肿瘤主要基于其独特的作用机制能 触发宿主抗肿瘤免疫作用，以及部分细菌能靶向性定植于肿瘤内部的特点，在实体肿瘤的基础研究和临床研究中均取得令人鼓 舞的疗效。综述就工程化细菌在肿瘤免疫治疗中的具体策略以及一些临床试验研究进行整理，讨论细菌疗法目前所面临的挑战 及应对策略等，以期为进一步的研究奠定基础，推进细菌在肿瘤治疗中的临床应用。
目前，肿瘤治疗方法日趋多样，其中细菌治疗渐成近年来的研究热点。细菌治疗肿瘤主要基于其独特的作用机制能 触发宿主抗肿瘤免疫作用，以及部分细菌能靶向性定植于肿瘤内部的特点，在实体肿瘤的基础研究和临床研究中均取得令人鼓 舞的疗效。综述就工程化细菌在肿瘤免疫治疗中的具体策略以及一些临床试验研究进行整理，讨论细菌疗法目前所面临的挑战 及应对策略等，以期为进一步的研究奠定基础，推进细菌在肿瘤治疗中的临床应用。
2022, 29(11):1054-1056.
DOI: 10.3872/j.issn.1007-385X.2022.11.018
Abstract:
肿瘤生物治疗学是生物医学相关各专业需要学习的课程，因其涉及医学免疫学、细胞与分子生物学、基因工程、药学 等多学科内容，综合性强，在教学中通常各学科各自为政，仅从本学科角度讲授某一部分知识，学生常有“门中窥物，难以见得全 貌”的困惑。针对当前教学模式中存在的问题，探索肿瘤生物治疗学专题课程的建设，在生物技术专业学生已具备相关学科知识 的基础上，基于PBL 理念对肿瘤生物治疗学专题课程的融合式教学进行初步探索，通过设计围绕肿瘤生物治疗产业链的“问题链”，通过分组讨论与协作探究解决方案，引导学生从全链条理解肿瘤生物治疗的开发与应用，培养科研思维；同时在教学中融合 多媒体教学与课程思政教学，以期激发学生的探索欲、提高积极性从而融会掌握课程内容。
肿瘤生物治疗学是生物医学相关各专业需要学习的课程，因其涉及医学免疫学、细胞与分子生物学、基因工程、药学 等多学科内容，综合性强，在教学中通常各学科各自为政，仅从本学科角度讲授某一部分知识，学生常有“门中窥物，难以见得全 貌”的困惑。针对当前教学模式中存在的问题，探索肿瘤生物治疗学专题课程的建设，在生物技术专业学生已具备相关学科知识 的基础上，基于PBL 理念对肿瘤生物治疗学专题课程的融合式教学进行初步探索，通过设计围绕肿瘤生物治疗产业链的“问题链”，通过分组讨论与协作探究解决方案，引导学生从全链条理解肿瘤生物治疗的开发与应用，培养科研思维；同时在教学中融合 多媒体教学与课程思政教学，以期激发学生的探索欲、提高积极性从而融会掌握课程内容。
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- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
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- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.