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1.
Article in English | WPRIM | ID: wpr-929017

ABSTRACT

OBJECTIVES@#Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer, with highmorbidity and mortality rate. Nove drug development for NSCLC is urgently needed.This study aims to investigate the activity of lathyrol derivatives and the mechanism for its inhibitory effect on the growth of NSCLC cells.@*METHODS@#Three lathyrol derivatives were synthesized from lathyrol and their structures were verified by nuclear magnetic resonance. MTT assay was used to detect the effects of the lathyrol derivatives on the proliferation activity of NSCLC cells (A549 and H1299 cells), and the compound with the best activity was selected for subsequent experiments. Colony forming assay, wound-healing assay, and transwell assay were applied to detect in vitro cell proliferation, migration and invasion ability in A549 and H1299 cells, respectively. Quantitative real-time RT-PCR and Western blotting were performed to detect mRNA and protein levels of E-cadherin, N-cadherin, β-catenin, and MMP2 in A549 cells, respectively.@*RESULTS@#Three lathyrol derivatives inhibited the growth of A549 and H1299 cells in a dose-dependent manner, and they showed a weak inhibitory effect on normal cells Beas-2B and 16HBE, indicating that they possessed certain selective toxic effects. Therefore, C-5 benzoylated lathyrol with the best activity was selected as the ideal drug for the subsequent experiments. Compared with the control group, the number and size of cell clusters in the treatment group of A549 and H1299 cells were significantly decreased, the relative mobility were significantly decreased, and the number of invaded cells were significantly decreased (all P<0.05), indicating that the in vitro cell proliferation, migration and invasion ability were decreased. The mRNA levels of integrin α2, integrin β1, MMP2, MMP9, β-catenin, and N-cadherin were decreased, while the expression of E-cadherin was increased (all P<0.05). The protein levels of N-cadherin, β-catenin, MMP2, and integrin αV were decreased, while the expression of E-cadherin was increased (all P<0.05).@*CONCLUSIONS@#The lathyrol derivatives synthesized in this study possess good inhibitory activity against NSCLC. Among them, C-5 benzoylated lathyrol significantly inhibits the proliferation, migration, and invasion ability of NSCLC cells in vitro through regulating the process of epithelial-mesenchymal transition.


Subject(s)
Cadherins/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition , Humans , Lung Neoplasms/drug therapy , Matrix Metalloproteinase 2/genetics , RNA, Messenger , beta Catenin/genetics
2.
Article in English | WPRIM | ID: wpr-929003

ABSTRACT

OBJECTIVES@#The advanced non-small cell lung cancer (NSCLC) patients with pleural effusion have no opportunity for surgery treatment. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line drugs for these patients with EGFR-sensitive mutation. However, the disease progression and drug update during or after treatment of EGFR-TKIs bring more challenges and puzzles to clinical diagnosis and treatment, which inevitably requires archived pleural cell samples for EGFR re-examination or comparative study. Understanding the DNA quality of archived pleural fluid samples and effectively using archival data of pleural fluid cells are of great significance for tracing the origin of cases and basic medical research. This study aims to evaluate the consistency of EGFR mutant gene expression between the 2 methods, and to explore a reliable way for preserving cytological data and making full use of cytological archival data via cell HE staining smear and cell paraffin section.@*METHODS@#A total of 57 pleural fluid cytology cases in the Department of Pathology of China Aerospace Center Hospital from October 2014 to April 2021 were selected. Tumor cells were detected by cell HE staining smears and immunohistochemical staining for TTF-1 and Napsin A in the paired cell paraffin sections. There were more than 200 tumor cells in cell HE staining smear and the proportion of tumor cells were ≥70% in matched cell paraffin sections. Patients with 2 cell smears (one for cell data retention and the other for DNA extraction) were selected as the research subjects, and 57 pleural fluid samples were enrolled. EGFR gene mutation was detected by amplification refractory mutation system-polymerase chain reaction in 57 paired cell HE staining smears and cell paraffin sections. DNA concentration was 2 ng/μL. Cell HE smear was amplified side-by-side with DNA samples from paired cell paraffin sections. Result determination was according to the requirements of the reagent instructions. The external control cycle threshold (Ct) value of the No. 8 well of the samples to be tested was between 13 and 21, which was considered as successful and reliable samples. When the Ct value of EGFR gene mutation was <26, it was considered as positive; when the Ct value was between 26 and 29, it was critical positive; when the Ct value was equal or more than 29, it was negative. ΔCt value was the difference between mutant Ct value and externally controlled Ct value. The smaller the ΔCt value was, the better the quality of DNA of the detected sample was.@*RESULTS@#Among the 57 pleural effusion samples, 42 patients were hospitalized with pleural effusion as the first symptom, accounting for 73.7% (42/57). EGFR mutation was detected in 37 samples [64.9% (37/57)]. The mutation rate for 19del was 37.8% (14/37) while for L858R was 48.6% (18/37). Females were 56.7% (21/37) of mutation cases. The mutation consistency rate of cell HE staining smear and matched cell paraffin sections was 100%. The ΔCt values of cell HE staining smears were less than those of matched cell paraffin sections. The mutation Ct values of 37 cytological samples were statistically analyzed according to the preservation periods of the years of 2014-2015, 2016-2017, 2018-2019, and 2020-2021. There were significant differences in cell paraffin section in the years of 2014-2015 and 2016-2017 compared with the years of 2018-2019 and 2020-2021, while no significant differences were found in cell HE staining smear. Statistical analysis of externally controlled Ct values of 57 cytological samples showed that there were significant differences between cell HE staining smears and cell paraffin section in the years of 2014-2015 and 2016-2017, compared with the years of 2018-2019 and 2020-2021. The mutational Ct values of 37 paired cell blocks and smears were all <26, and the externally controlled Ct values of 57 paired cell paraffin sections and HE staining smears were all between 13 and 21.@*CONCLUSIONS@#The DNA quality of cell HE smears and matched cell paraffin section met the qualified requirements. Two methods possess show an excellent consistency in detecting EGFR mutation in NSCLC pleural fluid samples. The DNA quality of cell HE staining smear is better than that of cell paraffin sections, so cell HE staining smear can be used as important supplement of the gene test source. It should be noted that the limitation of cell HE staining smears is non-reproducibility, so multiple smears of pleural fluid are recommended to be prepared for multiple tests.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , DNA Mutational Analysis/methods , ErbB Receptors/genetics , Female , Humans , Lung Neoplasms/drug therapy , Male , Mutation , Paraffin/therapeutic use , Pleural Effusion/genetics , Protein Kinase Inhibitors/therapeutic use , Staining and Labeling
3.
Chinese Journal of Lung Cancer ; (12): 506-510, 2022.
Article in Chinese | WPRIM | ID: wpr-939739

ABSTRACT

As lung cancer targeted therapy and immunotherapy drugs are the current hot spot in the research and development area of new anti-tumor drugs, the amount of clinical trial in this area is increasing year by year. On the basis of combing the on-site inspections of drug registration clinical trials from 2019 to 2021, combined with the characteristics of lung cancer targeted therapy and immunotherapy drugs, this paper discusses the focus of on-site inspection of clinical trials of such drugs, and puts forward suggestions for the compliant implementation of lung cancer clinical trials.
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Subject(s)
Antineoplastic Agents/therapeutic use , Humans , Immunologic Factors/therapeutic use , Immunotherapy , Lung Neoplasms/drug therapy , Molecular Targeted Therapy
4.
Chinese Journal of Lung Cancer ; (12): 501-505, 2022.
Article in Chinese | WPRIM | ID: wpr-939738

ABSTRACT

Clinical trials of anti-tumor drugs is not only the important way to develop new drugs, but also the most advanced treatment methods for malignant tumors, bringing survival benefits to patients. There are a large number of new anti-tumor drug clinical trials for lung cancer patients, covering a wide variety of anti-tumor drugs, and with rapid progress and high efficiency of clinical transformation. These trials could not be carried out successfully without the joint efforts of the research team, in which the research nurses also played a role that should not be underestimated. Combined with the work content of clinical research nurses, this paper introduced the post management, role function, core competence and career development prospect of clinical research nurses in the process of carrying out clinical trial of lung cancer drugs in detail. In order to provide reference for more medical institutions to carry out related work, and promote the further development of clinical research nurses to standardization and specialization.
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Subject(s)
Antineoplastic Agents/therapeutic use , Humans , Lung Neoplasms/drug therapy
5.
Chinese Journal of Lung Cancer ; (12): 468-476, 2022.
Article in Chinese | WPRIM | ID: wpr-939733

ABSTRACT

Antibody drug conjugates (ADCs) are a novel class of anti-cancer drugs, which combined the specificity of monoclonal antibodies with the cytotoxic palyload via the linkers. Many ADCs have not only verified impressive activity in a variety of cancers, including breast cancer and hematological system tumors, but also in lung cancer. The aim of this study was to provide informations for practice by summarizing the mechanism of action, clinical application and problems and challenges of ADCs.
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Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Humans , Immunoconjugates/therapeutic use , Lung Neoplasms/drug therapy , Neoplasms/drug therapy
6.
Chinese Journal of Lung Cancer ; (12): 448-451, 2022.
Article in Chinese | WPRIM | ID: wpr-939730

ABSTRACT

With the boom of China's innovative pharmaceutical industry, licensing-in model has gradually become an important research and development model for innovative pharmaceutical companies. The in-licensed drugs at different stages need different research and development (R&D) strategy in China. The pharmaceutical companies take the responsibility to comprehensively collate the oversea clinical data and conduct a detailed analysis of clinical pharmacology, safety, efficacy and ethnic sensitivity. Clinical R&D strategy should be made based on the results of the above data and analysis. We encourage high-quality drugs which fill unmet clinical needs licensed in, and as early as possible, so as to conduct multi-regional clinical trials (MRCTs). The clinical R&D strategy in China is particularly important for the drug's approval. Guidelines published by the National Medical Products Administration (NMPA) and clinical associations should be followed. Communications about clinical R&D strategy with Center of Drug Evaluation (CDE) are encouraged.
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Subject(s)
Antineoplastic Agents/therapeutic use , China , Drug Industry , Humans , Lung Neoplasms/drug therapy , Pharmaceutical Preparations
7.
Chinese Journal of Lung Cancer ; (12): 443-447, 2022.
Article in Chinese | WPRIM | ID: wpr-939729

ABSTRACT

In recent years, China's anti-tumor drugs has shown a continuous growth trend, and the activity of anti-tumor research and development in China accounts for a higher proportion in the world. However, further analysis of research and development hotspots show that the research and development of anti-tumor drugs is uneven among different tumor types. Due to the small number of the patients, it is difficult to conduct clinical trials, resulting in less drug development in the field of rare tumors. However, patients' treatment needs will also bring potential opportunities for pharmaceutical companies. The development of basic research and the discovery of new molecular tumor typing make "rare tumors" a dynamic concept. The scope of "rare tumors" may gradually expand with the precise development of treatment; or as the knowledge of tumors gradually develops from histocytology to the molecular level, It is possible that certain tumors with specific mutations can be combined into a group of non-rare "pan-tumors". Rare tumors are characterized by both rare diseases and tumors. Its drug research and development should not only meet the requirements of tumor drug research and development, but also adapt to the characteristics of rare diseases. Therefore, in the drug research and development, we can refer to the research and development principle of rare disease drugs, combine with the characteristics of tumor diseases, make full use of non-rare tumor clinical trials, make full use of scientific tools and exquisite trial design, and realize the promotion of the research and development of rare tumor drugs. This paper will summarize the thoughts in the review of new drugs in the field of rare tumors, in order to provide guidance for the industry.
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Subject(s)
Antineoplastic Agents/therapeutic use , China , Humans , Lung Neoplasms/drug therapy , Rare Diseases/drug therapy , Research
8.
Chinese Journal of Lung Cancer ; (12): 420-424, 2022.
Article in Chinese | WPRIM | ID: wpr-939726

ABSTRACT

Cachexia is a common complication in patients with lung cancer. It aggravates the toxic and side effects of chemotherapy, hinders the treatment plan, weakens the responsiveness of chemotherapy, reduces the quality of life, increases complications and mortality, and seriously endangers the physical and mental health of patients with lung cancer. The causes and pathogenesis of tumor cachexia are extremely complex, which makes its treatment difficult and complex. Controlling cachexia in lung cancer patients requires many means such as anti-tumor therapy, inhibition of inflammatory response, nutritional support, physical exercise, and relief of symptoms to exert the synergistic effect of multimodal therapy against multiple mechanisms of tumor cachexia. To date, there has been a consensus within the discipline that no single therapy can control the development of cachexia. Some therapies have made some progress, but they need to be implemented in combination with multimodal therapy after fully assessing the individual characteristics of lung cancer patients. This article reviews the application of drug therapy and nutritional support in lung cancer patients, and looks forward to the research direction of cachexia control in lung cancer patients.
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Subject(s)
Cachexia/therapy , Combined Modality Therapy , Humans , Lung Neoplasms/drug therapy , Neoplasms/complications , Nutritional Support/adverse effects , Quality of Life
9.
Chinese Journal of Lung Cancer ; (12): 401-408, 2022.
Article in Chinese | WPRIM | ID: wpr-939724

ABSTRACT

BACKGROUND@#Immunotherapy represented by immune checkpoint inhibitors (ICIs) has become the standard treatment for patients with non-oncogenic advanced non-small cell lung cancer (NSCLC). While lung cancer is most prevalent in elderly patients, these patients are rarely included in pivotal clinical trial studies. We aimed to describe the efficacy and safety of immunotherapy for elderly patients in the "real-world".@*METHODS@#The data of older NSCLC patients and younger patients who received immunotherapy between July 2018 to October 2021 were retrospectively analyzed and the objective response rate (ORR) and progression-free survival (PFS) in different age groups (less than 60 years old was defined as the young group, 60 years-74 years old was the young old group, 75 years old and above was the old old group) were compared. And the impact of different clinical characteristics on treatment response and prognosis were analyzed in each age subgroup.@*RESULTS@#A total of 21 young patients, 70 young old patients and 15 old old patients were included in this study, with ORR of 33.3%, 52.8% and 53.3%, respectively, without statistically significant difference (P=0.284). The median PFS was 9.1 mon, 7.6 mon and 10.9 mon, respectively, without statistically significant difference (P=0.654). Further analysis of the predictors of immunotherapy in each subgroup revealed that patients in the young old group and young group who received immunotherapy in the first line had a longer PFS. The difference of the incidence of adverse events was not statistically significant among the three groups (P>0.05).@*CONCLUSIONS@#The efficacy and safety of immunotherapy in elderly patients were similar to those in younger patients, and PFS was superior in the first-line immunotherapy. Further prospective studies are still needed to explore predictors of immunotherapy in elderly NSCLC patients.


Subject(s)
Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Immunotherapy/adverse effects , Lung Neoplasms/drug therapy , Middle Aged , Prognosis , Retrospective Studies
10.
Chinese Journal of Oncology ; (12): 112-119, 2022.
Article in Chinese | WPRIM | ID: wpr-935190

ABSTRACT

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Lung Neoplasms/drug therapy , Meningeal Carcinomatosis/drug therapy , Pemetrexed , Treatment Outcome
11.
Chinese Journal of Lung Cancer ; (12): 303-310, 2022.
Article in Chinese | WPRIM | ID: wpr-928813

ABSTRACT

BACKGROUND@#The expression of programmed cell death ligand 1 (PD-L1) as a biomarker for immunotherapy in non-small cell lung cancer (NSCLC) is routinely detected in clinical pathology department. However, the spatial heterogeneity of PD-L1 expression in intrapulmonary tumors and extrapulmonary metastases is still a challenge for the clinical testing. This study aims to explore the differences of PD-L1 expression in test samples obtaining from different sites of NSCLC. This study may contribute to the detection strategy of PD-L1 in patients with advanced lung cancer.@*METHODS@#One hundred and thirty-one cases of consecutively detected PD-L1 (22c3 assay, Dako) staining in metastatic NSCLC and 972 cases of non-paired intrapulmonary NSCLC were collected. The discrepancies of tumor proportion score (TPS) of PD-L1 expression in intrapulmonary samples and extrapulmonary metastatic samples of different sites were compared.@*RESULTS@#The positive expression rate of PD-L1 in extrapulmonary metastatic NSCLC (TPS ≥ 1%) was 61.83%, and the TPS was significantly higher than that in intrapulmonary tumors (P=0.03). The PD-L1 scores of the specimens obtained from different sites were significantly different (P=0.007). The positive rates of PD-L1 in liver and adrenal metastases were 85.71% and 77.78% respectively, and their TPS were significantly higher than that of the intrapulmonary samples (P<0.05). The positive rates of PD-L1 in lymph node, bone, brain, soft tissue, and pleural metastases was 40.00%-66.67%, with no significant differences compared to intrapulmonary tumors. The analysis of histological subtype and sample type showed that the PD-L1 score of extrapulmonary samples of adenocarcinoma subtype or surgical specimen was significantly higher than that of intrapulmonary tumors. The analysis of clinicopathological parameters showed that the PD-L1 positive expression or high expression were significantly correlated with male patients, smoking history, and epidermal growth factor receptor (EGFR) wild type.@*CONCLUSIONS@#The expression of PD-L1 in metastatic NSCLC is generally higher than that in intrapulmonary tumor, and the positive rate of PD-L1 expression was discrepant in different sites of specimen. The differences of PD-L1 score between extrapulmonary metastatic samples and intrapulmonary samples may be associated with different metastatic sites, histological subtype, and specimen type.


Subject(s)
B7-H1 Antigen/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Immunohistochemistry , Lung Neoplasms/drug therapy , Male
12.
Chinese Journal of Lung Cancer ; (12): 291-294, 2022.
Article in Chinese | WPRIM | ID: wpr-928811

ABSTRACT

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism for cerebral radiation necrosis (CRN) development. Antiangiogenic agents (Bevacizumab) alleviates brain edema symptoms caused by CRN through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that Bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients' performance status and brain necrosis imaging. Considering that the efficacy of antiangiogenic therapy is mainly related to the duration of drug action, low-dose antiangiogenic agents can achieve favorable efficacy. Prevention is the best treatment. The occurrence of CRN is associated with tumor-related factors and treatment-related factors. By controlling these factors, CRN can be effectively prevented.
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Subject(s)
Angiogenesis Inhibitors/pharmacology , Bevacizumab/therapeutic use , Brain/metabolism , Consensus , Humans , Lung Neoplasms/drug therapy , Necrosis/etiology , Radiation Injuries/etiology , Vascular Endothelial Growth Factor A/metabolism
13.
Chinese Journal of Lung Cancer ; (12): 259-265, 2022.
Article in Chinese | WPRIM | ID: wpr-928807

ABSTRACT

Patients with malignant pleural mesothelioma (MPM) usually present with poor prognosis and short survival period, and there has been a lack of effective treatment options for a long time. Chemotherapy has limited improvement in the clinical outcome of advanced patients (the median survival is less than one year), and it is difficult to find suitable targets for targeted therapy. Recent in-depth research on immunotherapy has changed the treatment pattern of MPM. Especially, the dual immunotherapy regimen significantly improved the survival outcome of patients across subgroups and prolonged the survival time of MPM patients. Therefore, it has been approved for unresectable MPM as first-line treatment for patients. The exploration of other mono or combo immunotherapy regimens in the first and second-line settings of MPM is also underway. How to identify the best beneficial population of each regimen through predictive biomarkers is also a hot spot for researchers. This article will focus on the most up-to-date progress of MPM epidemiology, histological characteristics, pathogenesis, treatment patterns and the advances of immunotherapy in the disease.
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Subject(s)
Combined Modality Therapy , Humans , Immunotherapy , Lung Neoplasms/drug therapy , Mesothelioma/drug therapy , Mesothelioma, Malignant , Pleural Neoplasms/drug therapy
14.
Chinese Journal of Lung Cancer ; (12): 214-218, 2022.
Article in Chinese | WPRIM | ID: wpr-928800

ABSTRACT

Lung cancer is one of the malignant tumors with the highest morbidity and mortality in the world. Non-small cell lung cancer (NSCLC) is one of the most important pathological types of lung cancer. The prognosis of advanced NSCLC is poor and medical treatment is still the main treatment option. Antibody-drug conjugates (ADCs) are the kind of potentially new anti-tumor drugs, consisting of monoclonal antibodies conjugated to the cytotoxic payloads via the synthetic linkers. They have a broad application prospect in solid tumors such as lung cancer. This article focuses on the mechanism of action and research progress of ADCs in advanced NSCLC.
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Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Immunoconjugates/therapeutic use , Lung Neoplasms/drug therapy
15.
Chinese Journal of Lung Cancer ; (12): 137-146, 2022.
Article in English | WPRIM | ID: wpr-928791

ABSTRACT

BACKGROUND@#The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear.@*METHODS@#A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization.@*RESULTS@#There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not.@*CONCLUSIONS@#In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.


Subject(s)
Camptothecin/therapeutic use , Glucuronosyltransferase/genetics , Humans , Lung Neoplasms/drug therapy , Mutation , Polymorphism, Genetic , Retrospective Studies
16.
Chinese Journal of Lung Cancer ; (12): 130-136, 2022.
Article in Chinese | WPRIM | ID: wpr-928790

ABSTRACT

Surgery is the standard treatment for resectable non-small cell lung cancer (NSCLC). Neoadjuvant and adjuvant therapy have been widely used for preventing recurrence and metastasis. Immune checkpoint inhibitors (ICIs) have brought long-term survival benefits in advanced NSCLC and showed higher downstage rates and pathological remission in the neoadjuvant setting. Predictive biomarkers are of great significance to identify the beneficiaries of neoadjuvant ICIs. At present, the biomarkers are still inconclusive. We summarized the clinical trials of neoadjuvant immune checkpoint inhibitors that have been disclosed so far, and reviewed the progress of the biomarkers associated with those trials.
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Subject(s)
Biomarkers , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Immune Checkpoint Inhibitors , Lung Neoplasms/drug therapy , Neoadjuvant Therapy
17.
Chinese Journal of Lung Cancer ; (12): 102-110, 2022.
Article in Chinese | WPRIM | ID: wpr-928786

ABSTRACT

Programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors and PD-1 inhibitors plus chemotherapy combination regimens have been widely used in the first-line treatment of advanced non-small cell lung cancer(NSCLC), but patients with low PD-L1 expression have limited objective response and survival benefits. Existing treatment regimens are still difficult to fully meet the clinical needs of patients in the real world. Therefore, researchers are still exploring novel superactive treatment options to further improve the efficacy and survival prognosis of different sub-groups in NSCLC. Dual immunotherapy [such as the combination of PD-1 and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) inhibitors] has shown considerable long-term survival benefits in a variety of tumors and has also shown broad clinical prospects in NSCLC. In addition to exploring different emerging combination options, how to accurately identify the optimal-benefit groups through predictive biomarkers and how to effectively manage the safety of combination immunotherapy through multidisciplinary collaboration are also the focus of dual immunotherapy. This article reviews the mechanism of action, research progress, predictive biomarkers and future exploration directions of dual immunotherapy.
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Subject(s)
B7-H1 Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Immunotherapy , Lung Neoplasms/drug therapy , Prognosis
18.
Chinese Journal of Lung Cancer ; (12): 92-101, 2022.
Article in Chinese | WPRIM | ID: wpr-928785

ABSTRACT

The emergence of immune checkpoint inhibitors (ICIs) has dramatically changed the therapeutic outlook for patients with non-small cell lung cancer (NSCLC). Preoperative neoadjuvant immunotherapy has been paid more and more attention as an effective and safe treatment. Neoadjuvant immune therapy, however, the relevant research started late, relatively few research results and mainly focused on the small sample size of phase I and II studies, treatment itself exists many places it is not clear, also in benefit population screening, the respect such as the choice of treatment and curative effect prediction has not yet reached broad consensus. This paper reviews the important studies and recent achievements related to neoadjuvant immunotherapy, aiming to comprehensively discuss the procedures and existing problems of this kind of therapy from three aspects of beneficiary groups, treatment cycle and efficacy prediction.
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Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Immune Checkpoint Inhibitors , Immunotherapy/methods , Lung Neoplasms/drug therapy , Neoadjuvant Therapy
19.
Article in Chinese | WPRIM | ID: wpr-928781

ABSTRACT

BACKGROUND@#Primary lung squamous carcinoma that produces alpha-fetoprotein (AFP) is rare and only four related cases have been reported so far. The specific reasons for elevated serum level of AFP and effective treatment regimens for AFP-producing lung squamous carcinoma are not clear. This paper reports the diagnosis and treatment of AFP-producing lung squamous carcinoma so as to provide some references for similar cases in clinical practice.@*METHODS@#The diagnosis and treatment of an AFP-producing lung squamous carcinoma patient admitted to the Shandong Cancer Hospital on October 23, 2020 was retrospectively analyzed, and literatures were reviewed.@*RESULTS@#A 52-year-old male patient was diagnosed as T4N3M0 stage, IIIc right upper lobe lung squamous cell carcinoma with mediastinal lymph node metastasis and multiple metastases in the lung. The main tumor marker was abnormally increased serum AFP. After the rapid progression of two lines chemotherapy, the patient was given anlotinib combined with carrizumab as third-line treatment. The efficacy evaluation reached to partial response (PR) and stable disease (SD) after 2 and 4 cycles of treatment, respectively. The treatment regimen was replaced with albumin paclitaxel plus carrizumab due to gastrointestinal bleeding after the fifth cycle. The patient's condition was under continuous control.@*CONCLUSIONS@#The AFP-producing lung squamous carcinoma patient had a good response to anlotinib and immunotherapy in the case report, which may provide some guidances for the clinical practice and the research on AFP-producing lung squamous carcinoma.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell/drug therapy , Humans , Lung , Lung Neoplasms/drug therapy , Male , Middle Aged , Retrospective Studies , alpha-Fetoproteins
20.
Article in Chinese | WPRIM | ID: wpr-928780

ABSTRACT

Immune checkpoint inhibitors (ICIs) are widely used in clinic, and the incidence of rare adverse events are increasing. The aim of this paper is to better define the rare adverse effect of diabetes mellitus associated with ICIs. We report 2 cases of diabetes mellitus associated with ICIs. Literature review was conducted and we discussed the clinical presentation, potential mechanisms and suggestions for optimal management. Two patients were both elderly women, case 1 had increased blood glucose after 7 months of using Durvalumab, and cases 2 had diabetic ketoacidosis after 6 weeks of using Pembrolizumab. Both patients were administered exogenous insulin to control blood glucose. Case 1 has been treated with Durvalumab until now and case 2 discontinued using of Pembrolizumab. HLA genotypes and other factors may explain the risk factors of diabetes associated with ICIs in some individuals. Diabetes mellitus associated with ICIs is an uncommon but potentially life-threatening endocrine system adverse event, which requires doctors to be vigilant. The patients who use ICIs need to monitor blood glucose. If they have hyperglycemia, endocrinologists should be asked to assist in diagnosis and treatment.
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Subject(s)
Aged , Blood Glucose , Diabetes Mellitus/drug therapy , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Lung Neoplasms/drug therapy
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