1.EGFR Mutation Status and PD-L1 Expression in Patients ≤40 Years Old with NSCLC
Mingming HU ; Zichen LIU ; Hongmei ZHANG ; Baohua LU ; Jie LI ; Qunhui WANG ; Fanbin HU ; Haifeng LIN ; Baolan LI ; Tongmei ZHANG
Cancer Research on Prevention and Treatment 2022;49(7):687-691
Objective To retrospectively analyze the clinical data of 47 young NSCLC patients mutation style of EGFR and PD-L1 expression in tumor cells, to understand their clinicopathological and molecular characteristics. Methods We enrolled 47 young (≤40 years old) patients confirmed as NSCLC who underwent surgical resection, and 94 old patients (≥60 years old) were matched as 1:2 by R language. EGFR mutation status was detected by ARMS-PCR, and the expression of PD-L1 was detected by immunohistochemistry. Results The median age of 47 young patients with NSCLC was 37 years old. The disease was more common in women and the majority type was adenocarcinoma. In youth group, the 19del and 20ins were more frequent, but the exon 21 L858R point mutation proportion was higher in elder group. The expression of PD-L1 was significantly increased in the solid predominant histological subtype. The PD-L1 expression in 19del patients was higher than that in the patients with L858R mutation in youth group. Conclusion The majority of young NSCLC patients are female, nonsmokers and suffered from adenocarcinoma cancer. The proportion of EGFR alteration in 19del and 20ins in youth group is higher than that in elder group. The positive rate of PD-L1 expression in solid predominant histological subtype is higher than that with other subtypes. The expression of PD-L1 in young patients with EGFR 19del is higher than that with L858R.
2.Expression of CD44 in Tumor Tissue and Serum of Small Cell Lung Cancer and Its Clinical Prognostic Significance.
Ying WANG ; Yi GUO ; Haifeng LIN ; Lina ZHANG ; Hongmei ZHANG ; Qunhui WANG ; Fanbin HU ; Jie LI ; Baolan LI ; Tongmei ZHANG
Chinese Journal of Lung Cancer 2021;24(8):583-590
BACKGROUND:
Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid growth, early metastasis and acquired therapeutic resistance, and the prognosis is extremely poor. Studies have proved that the stem cell marker CD44 is correlated with tumor recurrence and treatment resistance, however, there are limited reports yet concerning on the CD44 expression and its clinical prognostic significance in SCLC patients. The purpose of this study is to investigate the expression of CD44 in tumor tissues as well as serum of SCLC patients and explore its correlation with the clinical characteristics, therapeutic effect and prognosis.
METHODS:
The tumor tissues and serum samples of 47 newly diagnosed SCLC patients were collected. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to detect CD44. The relationship between CD44 level and the clinical characteristics as well as prognosis of the patients was analyzed.
RESULTS:
The stem cell marker CD44 was detectable both in serum sample and tumor tissue of SCLC patients. The positive rate of CD44 in tumor tissue was significantly higher in patients with performance status (PS) 2 than that of patients with PS 0-1 (85.71% vs 30%, P=0.017). Patients were divided in to different groups according to the treatment efficacy. The CD44 immunohistochemical score and serum level in the disease progression group were significantly higher than those in the disease control group, and the differences were statistically significant (P=0.006, P=0.034), Univariate analysis depicted that the progression-free survival (PFS) of CD44 positive patients was significantly shorter than that of CD44 negative patients (5.23 mon vs 9.03 mon, P=0.036).
CONCLUSIONS
The positive expression of CD44 in tumor tissues of pre-treatment SCLC patients is correlated with poor PFS. The clinical significance of CD44 is worthy to be further studied.
3.A Single Center Analysis of Advanced Non-small Cell Lung Cancer Patients Treated with Immunotherapy in Real-world Practice.
Yanxia LIU ; Tongmei ZHANG ; Yuan GAO ; Yang QU ; Baohua LU ; Hongmei ZHANG ; Qunhui WANG ; Jie LI ; Fanbin HU ; Baolan LI
Chinese Journal of Lung Cancer 2019;22(11):687-695
BACKGROUND:
In recent years, a number of clinical trials have shown that immunocheckpoint inhibitors (ICI) have brought survival benefits to patients with advanced non-small cell lung cancer (NSCLC), however, such clinical trials comprise cohorts selected based on strict and complex entry and exclusion criteria, and the results cannot fully reflect the real world situation. The purpose of this study was to investigate the clinical efficacy and safety of immunotherapy in the real world, as well as possible prognostic factors.
METHODS:
Patients with advanced NSCLC receiving immunotherapy in Beijing Chest Hospital from January 2017 to July 2019 were retrospectively collected, and the following information were collected: curative effect, progression-free surival (PFS) and adverse reactions. The occurrence of adverse reactions and clinical curative effect and prognosis factors that may be relevant were explored.
RESULTS:
34 patients were enrolled in this study, median PFS was 5.66 months (95%CI: 4.48-6.84), grade 1-2 and 3-4 incidence of adverse events was 61.71% (22/34) and 14.71% (5/34), there were 3 patients (8.82%) experienced fatal immune related adverse events (irAE), 2 cases were immune associated pneumonia, 1 case was immune related myocarditis. Univariate analysis showed that tumor-node-metastasis (TNM) stage and metastatic site were correlated with median PFS (P<0.05), and multivariate analysis showed that patients with extrapulmonary metastasis (OR=6.42, P=0.029) and pleural metastasis (OR=14.14, P=0.006) had shorter median PFS.
CONCLUSIONS
In the real world, immunotherapy has good efficacy in patients with advanced NSCLC, but the incidence of severe irAE is also higher. Distant metastasis and pleural metastasis are poor prognostic factors for advanced NSCLC patients receiving immunotherapy.
4.Serum CYFRA21-1 is Correlated with the Efifcacy of Epidermal Growth Factor Re-ceptor-tyrosine Kinase Inhibitor in Non-small Cell Lung Cancer Patients Harboring EGFR Mutations
WANG QUNHUI ; ZHENG HUA ; HU FANBIN ; ZHANG HONGMEI ; HU YING ; LI JIE ; ZHANG TONGMEI ; LIU ZAN ; LU BAOHUA ; HU AIMIN ; LI BAOLAN
Chinese Journal of Lung Cancer 2016;19(8):550-558
Background and objectiveEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard ifrst-line treatment regimen forEGFR mutated non-small cell lung cancer (NSCLC) patients. However, the ef-ifcacy of EGFR-TKIs widely varies. hTe aim of this study is to determine whether the pretreatment serum cytokeratin-19 frag-ments (CYFAR21-1) and carcinoembryonic antigen (CEA) are associated with the effcacy of EGFR-TKIs inEGFR-mutated NSCLC patients.MethodsWe retrospectively enrolled 194 NSCLC patients harboringEGFR mutations who received EGFR-TKIs. Clinical characteristics were collected, and the relation between the effcacy of EGFR-TKIs and pretreatment serum CYFAR21-1 and CEA was analyzed.Results In all cases, progression-free survival (PFS) in patients with high CYFAR21-1 level was signiifcantly shorter than PFS in patients with normal CYFAR21-1 (7.0vs 11.9 months,P<0.001). Overall survival (OS) in patients with high CYFAR21-1 was signiifcantly shorter than in the normal-CYFAR21-1 group (12.6vs28.0 months, P<0.001). In adenocarcinoma patients, PFS in the high-CYFAR21-1 level group was signiifcantly shorter than in patients with normal CYFAR21-1 (7.0vs 12.0 months,P<0.001). OS in patients with high CYFAR21-1 was signiifcantly shorter than that in the normal-CYFAR21-1 group (13.1vs 28.1 months,P<0.001). Among squamous carcinoma patients, CYFAR21-1 level did not affect survival. No signiifcant difference in PFS and OS was observed between patients with high CEA and patients with normal CEA.ConclusionEGFR-mutated patients with high CYFAR21-1 had signiifcantly shorter PFS and OS than patients with normal CYFAR21-1 atfer receiving EGFR-TKIs. Pretreatment serum CYFR21-1 level was a predictive marker of EGFR-TKI treatment inEGFR-mutated NSCLC patients.
5.Diagnosis of isolated fetal renal pyelectasis during midtrimester and follow-up the outcome in utero by prenatal ;ultrasonography
Chen ZHU ; Yunyun REN ; Yingliu YAN ; Li SUN ; Fanbin KONG ; Wei ZHAO ; Yanlai HU ; Ying YAO ; Ru LIN ; Beibei DAI
Chinese Journal of Ultrasonography 2015;(8):697-700
Objective To assess the clinical significance of fetal pyelectasis and its changing in utero. Methods One hundred and ninty-seven isolated pyelectasis cases were retrospective reviewed from Jan 2012 to Jul 2014.Isolated pyelectasis was defined as a renal pelvis anteroposterior diameter (RPAPD)of ≥5 mm without other fetal anomaly in second trimester.Persistent or progressive pyelectasis was defined as a RPAPD of ≥10 mm before delivery.They were divided into two groups according to the size of renal pelvis in second trimester:group A (RPAPD 5 - 10 mm)and group B (RPAPD ≥ 10 mm).As the same,there were two groups after 32 weeks of gestation:group C (RPAPD < 10 mm)and group D (RPAPD ≥ 10 mm).Results Totally 1 54 cases were followed up.There were 1 88 cases (95.4%)in group A,with 41 cases lost,141 cases (95.9%)RPAPD <10 mm,6 cases (4.1 %)RPAPD ≥10 mm before delivery.There were 9 cases (4.6%)in group B,with 2 cases lost,remained 7 cases RPAPD ≥ 10 mm before delivery. Conclusions Although most of the fetuses with RPAPD 5 - 10 mm in second trimester will remain the same or resolved before delivery,those with RPAPD ≥ 10 mm may persistent or progress.Prenatal assessment of fetal renal pelvis may provide properly consultation.
6.Clinical analysis of standardized drug treatment of cancer pain at the pain clinic
Heling SHI ; Xuebing LI ; Tongmei ZHANG ; Fanbin HU ; Jialin LU ; Qiyi MENG ; Baolan LI
Chinese Journal of Clinical Oncology 2013;(24):1506-1508
Objective: To observe the efficacy and safety of analgesic drugs in the standardized treatment of cancer pain patients at the pain clinic. Methods: The data of 787 cancer pain patients and their corresponding prescriptions for cancer pain were collected from April, 2012 to April, 2013 at the pain clinic. The obtained information comprise of diseases that lead to cancer pain, cause of pain, pain intensity, and efficacy and side effects of medications. Diseases that caused cancer pain include 658 cases with primary malignant lung cancer. Results: Pain was mainly caused by primary lung cancer in 787 cancer-related patients. An analgesic drug, namely, oxycodone hydrochloride, was administered in 54.6% via single drug therapy. The daily dosage range of this drug was 20 to 90 mg/d in 280 cases. About 35.6% of the studied patients with a daily dosage of 90 mg/d or lower had their pain effectively managed. After the treatment, the number of cases with moderate to severe pain was reduced from 437 (55.5%) to 248 (31.5%). The oral administration of opioid oxycodone hydrochloride tablets ranked first among the prescribed drugs for cancer pain, and single-drug therapy was the choice of medication. The majority of patients had satisfactory pain-relief with a daily dosage of less than 90 mg/d upon the administration of oxycodone hydrochloride sustained-release tablets and morphine sulfate controlled-release tablets. Side effects included mild constipation, nausea, vomiting, dizziness, loss of appetite, urinary retention, somnolence, and so on. Intervention treatment was needed in most of the patients. Conclusion: Pain clinic is critical in the administration of standardized treatment for cancer pain in hospitals. The establishment of pain clinic ensures the standardized treatment of cancer pain.
7.Effect of TGF-β1 and CTGF on skeletal muscle fibrosis in nerve compression
Zhongwei JIA ; Jianghai CHEN ; Yanhua CHEN ; Rui HU ; Fanbin MENG ; Yuxiong WENG ; Zhenbing CHEN
Chinese Journal of Microsurgery 2012;35(2):135-138,后插5
ObjectiveTo investigate expression of TGF-β1,CTGF and collagen deposition in skeletal muscle during chronic entrapment of peripheral nerve. MethodsFifty rats were separated into two groups,control group and experimental group. At different time points after operation, the right gastrocnemius of 5rats from each group were collected for further analysis such as HE, Masson stain, immunohistochemical staining,RT-PCR and Western-blot. Results It was observed that axon degeneration occurred during chronic nerve entrapment,and which was in line with reports from other groups.Moreover,it had been demonstrated that after nerve entrapment,skeletal muscles may form fibrosis and degeneration consequently.Within this pathological procedure,expression of TGF-β1. CTGF and deposition of collagenⅠ changed rapidly when compared with control group.ConclusionOverall,these results indicated that these factors may be important during skeletal muscle degeneration after chronic nerve entrapment.
8.Expression and role of connective tissue growth factor in the peripheral nerve after chronic compression injury
Rui HU ; Zhenbing CHEN ; Zhongwei JIA ; Fanbin MENG ; Jie LAO
Chinese Journal of Microsurgery 2012;35(4):294-298,后插5
Objective To investigate the effects of connective tissue growth factor (CTGF) on the chronic peripheral nerve compression injury and explore the function of CTGF in peripheral nerve compression injury and repair. Methods From July 2010 to September 2010, fifty aduh male SD rats were randomly divided into group A and B: group A (sham-operated group): only exposed the sciatic nerve; group B (compression group): undergone sciatic nerve entrapment operation on the right hind leg according to the method which Mackinnon adopted when he established the model of chronic sciatic nerve compression.Electron microscopy,immunohistochemistry,RT-PCR and Western-blot were performed to observe the morphological changes of the compressed nerve tissue and to determine the level of CTGF,collagen- Ⅰ,Ⅲ (COL- Ⅰ,Ⅲ),2,4,6,8,10 weeks after the surgery,respectively. Results After sciatic nerve compression,the collagen in nerve increased ; The expression of CTGF and COL- Ⅰ, Ⅲ in sciatic nerve of compressed group increased, which was statistically different compared with the sham-operation group (P < 0.05); In the meanwhile,the contents of CTGF and COL- Ⅰ,Ⅲ were positively correlated in a certain period. Conclusion Peripheral nerve fibrosis can be caused by chronic nerve compression.The expression of COL- Ⅰ,Ⅲ in sciatic nerve increased and CTGF get involved in the pathophysiological process, which suggests that CTGF plays an important role in the process of neural injury and fibrosis.
9.Role of iatrogenic transforming growth factor-β1 antibody in peripheral neural fibrosis after chronic entrapment
Rui HU ; Jie LAO ; Zhongwei JIA ; Fanbin MENG ; Zhenbing CHEN
Chinese Journal of Trauma 2011;27(9):816-821
ObjectiveTo investigate the effect of transforming growth factor-β1 (TGF-β1) antibody on peripheral neural fibrosis after chronic entrapment.MethodsA total of 75 rats were randomly divided into three groups, ie, Group A (sham operation, only the sciatic nerve exposed), Group B (compression only, treated with sciatic nerve entrapment) and Group C (compression plus antibody injection).Electron microscopy, immunohistoehemistry, RT-PCR and Western blot were performed to observe the morphological changes of the compressed nerve tissue and to determine the level of TGF-β1 , collagen Ⅰ and collagen Ⅲ at 2, 4, 6, 8, 10 weeks after sciatic nerve compression, respectively.Results The levels of TGF-β1 , types Ⅰ and Ⅲ collagen protein were increased significantly in the Group B compared with that in the Group A, when the expression of TGF-β1 was increased in the early phase of the compression, reached the peak at the 4th week, and then decreased slowly.The expressions of collagenⅠand collagen Ⅲ were increased after compression, reached a peak at the 6th week and then maintained a relatively high level.The number of the fibrous tissues was decreased significantly and the content of types Ⅰ and Ⅲ collagen protein declined in the Group C, with statistical difference compared with the Group B (P < 0.05).ConclusionsPeripheral nerve fibrosis can be caused by chronic nerve compression.TGF-β1 plays an important role in effectively inhibiting the collagen synthesis and ameliorating the nervous fibrosis of the protein following peripheral nervous entrapment.
10.A randomized study comparing topotecan plus cisplatin versus etoposide plus carboplatin for previously untreated small cell lung cancer.
Shucai ZHANG ; Jinghui WANG ; Qunhui WANG ; Hui ZHANG ; Fanbin HU ; Xinjie YANG ; Xiaofang FAN ; Haiyong WANG ; Yanfei GU ; Xi LI
Chinese Journal of Lung Cancer 2007;10(2):144-147
BACKGROUNDTopotecan is one of active agents for relapsed small cell lung can-cer (SCLC), some studies have shown that it is effective against SCLC as the first-line drug. This study is to assess the efficacy, toxicity and survival rate of topotecan plus cisplatin (TP) versus etoposide plus carboplatin (CE) in patients with previously untreated SCLC.
METHODSSixty-four patients with previously untreated SCLC were randomly assigned to receive either TP or CE. Topotecan 0.75 mg/(m²×d) via a 30-min intravenous infusion on days 1 to 5 and cisplatin 25 mg/(m²×d) on days 1 to 3 with hydration were given to patients in TP group. Carboplatin 300 mg/m² on day 1 and etoposide 100 mg/d on days 1 to 5 were given to patients in CE group. Treatment was repeated every 21 days. Responses and toxicities were evaluated in patients who received two cycles of chemotherapy. Patients with limited disease SCLC received thoracic irradiation or operation after the completion of chemotherapy.
RESULTSOverall response rate was 75.0% in TP group and 68.8% in CE group. The median survival time was 10.5 months in TP group and 9.6 months in CE group. 1-, 2- and 3-year survival rate were 40.6%, 18.8% and 9.4% in TP group and 34.4%, 15.6% and 9.4% in CE group respectively. There were no significant differences in response rate, median survival time and survival rate between two groups (P > 0.05). Myelosuppression, nausea and vomiting, and alopecia were the most common toxicities, there was no significant difference in grade III and IV toxicities between two groups (P > 0.05).
CONCLUSIONSTP has similar response rate and survivals with CE, and its toxicities are acceptable. TP regimen is an effective first-line treatment for SCLC.

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