Research on the Antitumor Effect of Plumbagin by Inhibiting IL-6/STAT3 Pathway in Large Cell Lung Cancer

Background and Objective Lung cancer, which has become the leading cause of tumor mortality in many countries, appears to be one of the most dangerous malignant tumors that

Alterations and Its Mechanisms of Wnt Signal Pathway in Human High-matastatatic Large Cell Lung Cancer Cell Line L9981 by Transfecting with Nm23-H1 Gene

Backgroud and Objective Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the main cause of failure to cure and lose their life of the

The Difference of the Copy Number Variation and Loss of Heterozygosity of Human Lung Large Cell Cancer Cell Line with Different Metastatic Potential

Background and Objective It has been proven that copy number gain/or loss (copy number variation CNV) in uences gene expression and result in phenotypic variation by

The Difference of Gene Expression Prof ile in Human Large Cell Lung Cancer Cell Lines with Different Metastatic Potential

Background and Objective Lung cancer is the most lethal malignangy that threatens human heath and lives nowadays in the world, and meanwhile is also the one with worst

The Effects of Intracellular Glutathione Content on the Sensitivity of Methylseleninic Acid to Human High-metastatic Large Cell Lung Cancer Cell Line L9981

Background and Objective Lung cancer has the fastest increasing rate of morbidity and mortality all over the world and appears to be one of the most dangerous malignant tumors

Down-regulation and It's Molecular Biology of Nm-23H1 gene Transfection on Ras-to-MAPK Signal Transduction Pathway in Human High-metastatic Large Cell Lung Cancer Cell Line L9981

Backgroud and Objective Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the key cause of failure to cure and lose their life of the patients

Role of positron emission tomography-computed tomography in non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell carcinoma and small cell carcinoma are the main histological subtypes and constitutes around 85% and 15% of all lung cancer respectively. Multimodality treatment plays a key role in the successful management of lung cancer depending upon the histological subtype, stage of disease, and performance status. Imaging modalities play an important role in the diagnosis and accurate staging of the disease, in assessing the response to neoadjuvant therapy, and in the follow-up of the patients. Last decade has witnessed voluminous upsurge in the use of positron emission tomography-computed tomography(PET-CT); role of PET-CT has widened exponentially in the management of lung cancer. The present article reviews the role of 18-fluoro-deoxyglucose PET-CT in the management of non small cell lung cancer with emphasis on staging of the disease and the assessment of response to neoadjuvant therapy based on available literature.

Feasibility of cetuximab and chemoradiotherapy combination in Chinese patients with unresectable stage Ⅲ non-small cell lung cancer:a preliminary report

Objective： In recent years, the combination of cetuximab and chemoradiotherapy （CRT） has been used to treat stage III non-small cell lung cancer （NSCLC）; however, limited data are available for Chinese patients. Herein, we report preliminary data from a phase I/II study testing the combination of cetuximab with inductive chemotherapy, followed by concurrent CRT （CCRT） in Chinese patients with stage III NSCLC. Methods： Eligibility criteria were Zubrod performance status （PS） 0-1, forced expiratory volume in 1 second （FEV1） 〉_1.2 L and adequate organ function. Enrolled patients received weekly cetuximab （initial dose of 400 mg/m2 on day 1 of week 1 and a maintenance dose of 250 mg/m2 on week 2 to the end of CCRT） with cisplatin/vinorelbine （NP） chemotherapy （every 3 weeks for 2 cycles from week 2, followed by two cycles of concomitant NP chemotherapy and intensity-modulated thoracic radiotherapy （TRT） （60-66 Gy/2 Gy）. The primary endpoints were toxicity and feasibility. All patients received positron emission tomography- computerized tomography （PET-CT） scans within the 2 weeks prior to enrollment. Univariate analyses were used to assess the correlation between SUV-T, SUV-N, SUV-TOTAL, gender, age, histology, tumor-node- metastasis （TNM） stage, PS and smoking status and survival. Survival curves were generated for different populations using the Kaplan-Meier method and compared using a log-rank test. Results： Seventeen patients were enrolled and 16 completed the full regime. The overall response rate （ORR） was 58.8% and 82.3% after the induction and CCRT phases, respectively. With a median follow-up duration of 27.6 months, the median survival was 27.6 months [95% confidence interval （CI）： 11.3-43.9 months] with 1- and 2-year survival rates of 88.2% （95% CI, 60.6-96.9%） and 58.8% （95% CI, 60.6-77.8%）, respectively. Three patients remain progression-free to date, and the median progression-free survival （PFS） was 13.5 months （95% CI, 6.8-20.2 months）. No treatment-related death occurred; however, 76% of the patients experienced grade 3＋ adverse events （AEs）, including nansea/vomiting, intestinal obstruction, and esophagitis （〈6%）, while other AEs were mostly of hematological nature （71%）. The cut-off values for SUV-T and SUV-TOTAL were 11 and 20, respectively. Univariate analyses revealed SUV-TOTAL （P=0.027）, SUV-T （P=0.025）, and PS （P=0.006） as potential survival predictors, with a hazard ratio （HR） of 3.4, 3.7, and 9.9, respectively. Conclusions： The combination of cetuximab with induction chemotherapy followed by CCRT appears feasible and promising. Local and locoregional maximal SUVs, defined by 18F-FDG PET-CT scanning, may represent a prognostic indicator for long-term survival for these patients, which warrants further study.

Prognostic Values of PET/CT Findings and Tumor/Patient Characteristics with Non-Small Cell Lung Cancer

Background/Aim: Although numerous prognostic factors have been described for non-small cell lung cancer (NSCLC), there is still a requirement for better and non-invasive markers. FDG-PET is a non invasive diagnostic tool that is being used increasingly in the diagnosis of lung cancer. This study evaluates the prognostic values of PET/CT defined SUV measurements and other patient/tumor characteristics in newly diagnosed stage IIIB and IV NSCLC. Method: This ret- rospective study included 111 patients admitted between 2005 and 2006 with stage IIIB and IV NSCLC, whose diag- noses were verified with biopsy and staging performed with PET/CT. The prognostic values of standart uptake values (SUV) of the primary lesion on PET/CT, and other patient/tumor characteristics were analyzed using survival analysis. Results: SUV was found to be unrelated with survival. Only the presence of distant metastasis, type of metastasis (bone, brain, or the contralateral lung) and the type of radiotherapy used (curative or palliative) were found to be related to survival. SUV values in epidermoid carcinoma were found to be significantly higher compared to adenocarcinoma (16.15 ± 7.18 and 12.32 ± 5.52, respectively, p = 0.021).Conclusion: Our findings do not support that SUV of the pri- mary lesion in inoperable NSCLC has a prognostic value with respect to survival. This condition may be explained by the inclusion of significantly advanced NSCLC patients who are known to have a low survival and a high mortality, and also the relatively small sampling size.

Screening for lung cancer with chest computerized tomography: Is it cost efficient?

Despite lung cancer(LC) screening by low-dose computerized tomography(LDCT) gaining many proponents worldwide, for many years it was not recognized as a life-prolonging and cost-effective procedure, until recently. Prospective observational studies had not been able to prove that this screening prolongs survival, but they helped to specify the inclusion and exclusion criteria. Long-awaited results of a prospective, randomized trial finally provided the evidence that LC screening with LDCT can prolong survival of the screened population. Several costeffectiveness analyses were performed to justify mass introduction of this screening. Results of these analyses are equivocal, although conclusions highly depend upon inclusion and exclusion criteria, methods of analysis and prices of medical procedures which differ between countries as well as the incidence of other pulmonary nodules, especially tuberculosis. Therefore, costeffectiveness analysis should be performed separately for every country. Cost-effectiveness depends especially upon the rate of false-positive results and the rate of unnecessary diagnostic, screening and treatment procedures. To ensure high cost-effectiveness, LC screening should be performed in accordance with screening protocol, in dedicated screening centers equipped with nodule volume change analysis, or as a prospective non-randomized trial, to ensure compliance with the inclusion and exclusion criteria. To ensure high cost-effectiveness of LC screening, future research should concentrate on determination of highrisk groups and further specifying the inclusion and exclusion criteria.

^(18)F-FETNIM PET/CT hypoxia imaging in non-small cell lung cancer:preliminary clinical observation

Objective:The aims of this study were to evaluate potential side effects of 18F-fluoroerythronitroimidazole (18F-FETNIM) as a new-type hypoxia-imaging agent and to investigate the feasibility of 18F-FETNIM PET imaging in advanced non-small cell lung cancer (NSCLC) patients and the correlations of hypoxia extent with tumor volume or pathological type. Methods: Twenty-six NSCLC patients were prospectively included in the study. PET/CT scans were performed 2 h after intravenous injection of 18F-FETNIM in all 26 patients. A pixel-by-pixel calculation of tumor to blood (T/B) activity ratio for all image planes was calculated. The number of pixels in the tumor volume with a T/B ratio≥ 1.5,indicating significant hypoxia,was determined and converted to mL units to measure the hypoxia volume (HV). Results: The images were clearly identified after 2 h post-injection of 18F-FETNIM. The tumors in 4 cases were not distinguished from background,while the remaining 22 displayed local 18F-FETNIM uptake in thoracic lesions moderately to markedly higher than background. There was no correlation between 18F-FETNIM uptake with pathological type. There were significant correlations of HV and also the T/B ratio with tumor volume. Conclusion:18F-FETNIM is a promising hypoxia-imaging agent which clinical use is safe and satisfactory. The preliminary study provides valuable methods and experience to its further research.

Treatment of Non-Small Cell Lung Cancer (NSCLC) Using CT in Combination with a PET Examination to Minimize the Clinical Target Volume of the Mediastinum

OBJECTIVE To decrease radiation injury of the esophagus and lungs by utilizing a CT scan in combination with PET tumor imaging in order to minimize the clinical target area of locally advanced non-small cell lung can-cer, without preventive radiation on the lymphatic drainage area. METHODS Of 76 patients with locally advanced non-small cell lung cancer (NSCLC), 32 received a PET examination before radiotherapy. Preventive radiation was not conducted in the mediastinum area without lymphatic metastasis, which was confirmed by CT and PET. For the other 44 patients, preventive radiation was performed in the lymphatic drainage area. PET examinations showed that the clinical target volume of the patients was decreased on average to about one third. The radiation therapy for patients of the two groups was the same, i.e. the dose for accelerated fractionated irradiation was 3 Gy/time and 5 time/week. The preventive dose was 42 to 45 Gy/time, 14 to 15 time/week, with 3-week treatment, and the therapeu- tic dose was 60 to 63 Gy/time, 20 to 21 time/week, with a period of 4 to 5 weeks. RESULTS The rate of missed lymph nodes beyond the irradiation field was 6.3% and 4.5% respectively in the group with and without PET exami- nation (P = 0.831). The incidence of acute radioactive esophagitis was 15.6 % and 45.5% in the two groups respectively (P = 0.006). The incidence of acute radiation pneumonia and long-term pulmonary fibrosis in the two groups was 6.3% and 9.1%, and 68.8% and 75.0%, respectively (P = 0.982 and P = 0.547). CONCLUSION The recurrence rate in the lymph nodes beyond the tar-get area was not increased after minimizing the clinical target volume (CTV), whereas radioactive injury to the lungs and esophageal injury was reduced, and especially with a significant decrease in the rate of acute radioactive esophagitis. The method of CT in combination with PET for minimizing the mediastinal CTV is superior to the conventional preventive radiation of the mediastinum.

¹⁸FDG-PET/CT Is a Useful Tool in Staging Procedure before Chemo-Radiotherapy in Patients with Limited Disease Small-Cell Lung Cancer. Pattern of Failure and Survival Is Analyzed

Background: The purpose of this study was to evaluate the use of 18FDG-PET/CT in staging procedure, the pattern of failure and survival in patients with small-cell lung cancer limited disease (LD-SCLC) undergoing chemo-radiotherapy. Methods: A total of 79 LD-SCLC patients were treated with a combination of chemotherapy and chest radiotherapy. Radiotherapy of the tumour and the pathological lymph nodes was performed either as 45 Gy twice-daily or 46 - 50 Gy once-daily. 18Fluro-2-deoxy-D-glucose (18FDG)-PET/CT was performed in 35 patients as part of the staging procedure. Results: With a median follow-up time of 17 months 6% developed isolated loco-regional failures while 57% developed distant metastases. No isolated regional failures were seen. Median overall survival was 22 months. Patients staged with a 18FDG-PET/CT had a significantly lower incidence of distant failures and a significantly improved overall survival compared with patients only staged with a CT scan (p = 0.03) (median overall survival of 34 versus 17 months, respectively). Conclusion: The pattern of failure showed a high risk of distant metastases but a low incidence of isolated loco-regional failures. Patients staged with an 18FDG-PET/CT had a significantly lower incidence of distant failures and better overall survival, indicating that 18FDG-PET could be beneficial in patients with LD-SCLC before deciding on treatment regimen.

Current status of Radiologic Diagnosis for Mediastinal Lymph Node Metastases of Non-Small-Cell Lung Cancer: Retrospective Study of pN2 Cases

Objective: Advances in diagnostic imaging techniques, such as 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), have led to greater accuracy in preoperative mediastinal staging for patients with non-small-cell lung cancer (NSCLC), but surgical staging remains the “gold standard” for diagnosis. A proper understanding of the current accuracy of diagnostic imaging is needed for further improvements. Methods: Forty-three patients who underwent resection for NSCLC involving mediastinal lymph node (MLN) metastasis at our hospital between June 2003 and May 2011 were enrolled in this study. We conducted a retrospective study of the radiological and pathological findings for 53 metastatic MLNs in the 43 patients. Results: The preoperative imaging modality was computed tomography (CT) alone for 18 patients (22 MLNs) and CT and FDG-PET for 25 patients (31 MLNs). The sensitivities of CT and FDG-PET were 41.5% and 58.0%, respectively. The sensitivity of CT did not differ according to any clinicopathological factors, but the sensitivity of FDG-PET tended to be higher for primary tumors with high SUVmax values and for non-adenocarcinomas. In the lymph nodes, all micrometastatic foci ≤ 2 mm were PET-negative, but 4 lymph nodes with metastatic foci larger than 10 mm were also PET-negative. Conclusions: For the diagnostic imaging of MLN, FDG-PET has a greater sensitivity than contrast-enhanced CT based on “size criteria”, but it is still not sufficiently sensitive and is influenced by various factors. At present, histological confirmation of MLNs is necessary when making decisions regarding treatment plans and the type of surgical procedure that should be performed.

Lung squamous cell carcinoma presenting as rare clustered cystic lesions:A case report and review of literature

BACKGROUND Lung cancer is the leading cause of cancer-related death.Early diagnosis is critical to improving a patient’s chance of survival.However,lung cancer associated with cystic airspaces is often misdiagnosed or underdiagnosed due to the absence of clinical symptoms,poor imaging specificity,and high risk of biopsy-related complications.CASE SUMMARY We report an unusual case of cancer in a 55-year-old man,in which the lesion evolved from a small solitary thin-walled cyst to lung squamous cell carcinoma(SCC)with metastases in both lungs.The SCC manifested as rare clustered cystic lesions,detected on chest computed tomography.There were air-fluid levels,compartments,and bronchial arteries in the cystic lesions.Additionally,there was no clear extrathoracic metastasis.After chemotherapy,the patient achieved a partial response,type I respiratory failure was relieved,and the lung lesions became a clustered thin-walled cyst.CONCLUSION Pulmonary cystic lesions require regular imaging follow-up.Lung SCC should be a diagnostic consideration in cases of thin-walled cysts as well as multiple clustered cystic lesions.

FDG-PET for predicting efficacy of EGFR-tyrosine kinase inhibitors in lung cancer

Non-small cell lung cancer(NSCLC) is the major cause of cancer-related deaths worldwide. Recent advances in molecular biology have resulted in the clinical use of several molecularly targeted drugs, which usually exhibit cytostatic antitumor activity, to improve the survival of NSCLC patients. The epidermal growth factor receptortyrosine kinase inhibitors(EGFR-TKIs) gefitinib and erlotinib have been approved for the treatment of NSCLC, and several phase Ⅲ trials have demonstrated that sensitizing EGFR mutations are biomarkers for predicting a favorable clinical outcome of NSCLC patients treated with the EGFR-TKIs. The Response Evaluation Criteria in Solid Tumors is generally used to assess the therapeutic response to antitumor drugs based on the morphological changes in tumor size as evaluated by computed tomography or magnetic resonance imaging. However, such assessment may not always reflect the treatment efficacy of cytostatic drugs, such as EGFR-TKIs. In this regard, functional imaging methods, including 18F-fluorodeoxyglucose measured by positron emission tomography(FDG-PET), are potentially beneficial. An increasing body of evidence indicates the usefulness of FDG-PETto predict treatment efficacy for NSCLC patients treated with EGFR-TKIs. In this review, we summarize the current understanding of the potential role of FDG-PET in the clinical use of EGFR-TKIs for NSCLC.

Computed tomography-based delta-radiomics enabling early prediction ofshort-term responses to concurrent chemoradiotherapy for patients withnon-small cell lung cancer

Objective:To explore the potential of computed tomography(CT)-based delta-radiomics in predicting early shortterm responses to concurrent chemoradiotherapy for patients with non-small cell lung cancer(NSCLC),in order to determine the optimal time point for the prediction.Methods:A total of 20 patients with pathologically confirmed NSCLC were prospectively enrolled in this study,who did not receive surgical treatment between February 2021 and February 2022.For each case,a total of 1,210 radiomic features(RFs)were extracted from both planning CT(pCT)images along with each of the subsequent three weeks of CT images.EffectiveΔRFs were selected using intra-class correlation coefficient(ICC)analysis,Pearson's correlation,ANOVA test(or Mann-Whitney U-test),and univariate logistic regression.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve was used to evaluate the potential to predict short-term responses of different time points.Results:Among the 1,210ΔRFs for 1-3 weeks,121 common features were retained after processing using ICC analysis and Pearson's correlation.These retained features included 54 and 58 of all time points that differed significantly between the response and non-response groups for the first and third months,respectively(P<0.05).After univariate logistic regression,11 and 44 features remained for the first and third months,respectively.Finally,eightΔRFs(P<0.05,AUC=0.77-0.91)that can discriminate short-term responses in both at 1 and 3 months with statistical accuracy were identified.Conclusion:CT-based delta-radiomics has the potential to provide reasonable biomarkers of short-term responses to concurrent chemoradiotherapy for NSCLC patients,and it can help improve clinical decisions for early treatment adaptation.

Inhalable oridonin-loaded poly(lactic-co-glycolic)acid large porous microparticles for in situ treatment of primary non-small cell lung cancer

Non-small cell lung cancer(NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic-co-glycolic)acid(PLGA) large porous microparticle(LPMP) for in situ treatment of NSCLC with the emulsion/solvent evaporation/freeze-drying method. The LPMPs were smooth spheres with many internal pores. Despite a geometric diameter of 10 mm, the aerodynamic diameter of the spheres was only 2.72 mm, leading to highly efficient lung deposition. In vitro studies showed that most of oridonin was released after 1 h, whereas the alveolar macrophage uptake of LPMPs occurred after 8 h, so that most of oridonin would enter the surroundings without undergoing phagocytosis. Rat primary NSCLC models were built and administered with saline, oridonin powder, gemcitabine, and oridonin-loaded LPMPs via airway, respectively. The LPMPs showed strong anticancer effects. Oridonin showed strong angiogenesis inhibition and apoptosis. Relevant mechanisms are thought to include oridonin-induced mitochondrial dysfunction accompanied by low mitochondrial membrane potentials, downregulation of BCL-2 expressions, upregulation of expressions of BAX, caspase-3 and caspase-9. The oridonin-loaded PLGALPMPs showed high anti-NSCLC effects after pulmonary delivery. In conclusion, LPMPs are promising dry powder inhalations for in situ treatment of lung cancer.

The Relationship between Serum VEGF Expression and PET/CT Images in TNM-staging of Lung Carcinoma

OBJECTIVE To analyze the relationship between the characteristics of PET/CT images for lung carcinoma(LC)TNM staging and the expression of serum VEGF protein. METHODS PET/CT examinations were performed before treatment of 53 patients with LC.The expression of serum VEGF protein was examined using a quantitative sandwich enzyme-linked immunosorbent assay(ELISA R and D system).The relationship was analyzed between PET/CT images for LC T-staging and metastasis(lymph nodes and distance)and serum VEGF expression. RESULTS Based on PET/CT images for LC T-staging,11 cases were staged as T1,9 as T2,18 as T3 and 15 as T4.Mediastinal nodal metastases were found in 22 patients,and distance metastasis in 9.The serum VEGF level in the LC patients was(378.02±180.79)ng/L,showing that there was a significant difference between the patients and healthy subjects(P<0.05). There was no significant difference in the level of serum VEGF between different low T-staged(T1,T2)patients.However,the level of serum VEGF was significantly different between the low T-staged(T1,T2)and high T-staged (T3,T4)patients(P<0.05).The level of the serum VEGF protein in the patients with mediastinal nodal metastasis was(561.50±104.55)ng/L,and indicating that there was a statistical significance(t=12.21,P<0.05)compared to those in the non-metastatic group.The level of serum VEGF in the patients with distance metastasis was(614.11±158.81)ng/L,demonstrating that there was a significant difference(t=5.30,P<0.05)compared to those in the nondistant metastatic group. CONCLUSION ① There is a high level of serum VEGF expression in LC patients.②There is a correlation between metastases(lymph nodes and distance)and the level of serum VEGF. ③ With an upgrade of the TNM-stage,the level of serum VEGF protein is elevated.

体重指数对Ⅲ/Ⅳ期非小细胞肺癌患者冷冻消融术后生存期的影响

目的探讨体重指数(BMI)与接受冷冻消融治疗的Ⅲ/Ⅳ期非小细胞肺癌(NSCLC)患者的生存期关系。方法回顾性分析49例接受CT引导下冷冻消融治疗的Ⅲ/Ⅳ期NSCLC患者的临床资料。对BMI与消融术后生存期(COS)进行了相关性分析。结果49例患者中,体重不足者3例,正常体重者33例,超重者13例,肥胖者0例。体重不足组、正常体重组、超重组平均COS分别为11.00月、10.79月,17.08月。LSD法两两比较,正常体重组与超重组COS差异有统计学意义,P=0.013<0.05。Spearman相关分析示,分期(r=-0.355,P=0.015<0.05)、BMI(r=0.399,P=0.006<0.05)与患者消融后生存期有相关关系;控制分期后行偏相关分析,BMI仍与COS存在相关(r=0.327,P=0.028<0.05)。结论BMI与冷冻消融治疗Ⅲ/Ⅳ期NSCLC患者的生存期独立相关,高BMI的患者COS更长。