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Background: Anaplastic lymphoma kinase (ALK) test in advanced non-small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC., Methods: In this real-world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)-VENTANA-D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well., Results: The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC-VENTANA-D5F3 revealed an intra-hospital consistency rate of 98.2% (879/895) and an inter-hospital consistency rate of 99.2% (646/651). IHC-VENTANA-D5F3 was used in 53.6%, real-time polymerase chain reaction (RT-PCR) in 25.4%, next-generation sequencing (NGS) in 18.3%, and fluorescence in-situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT-PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05)., Conclusions: This study highlights the real-world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC-VENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC., (© 2024 The Author(s). Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of Sun Yat‐sen University Cancer Center.)

A meta-analysis was performed to comprehensively assess the effects of video-assisted thoracoscopy on surgical site wound infection and wound pain in patients with lung cancer. Studies on video-assisted thoracoscopy for lung cancer were collected from PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang database, from inception to January 2023. Two researchers independently screened the literature, extracted the data, and evaluated the quality of the included studies according to the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. Thirty-one articles with a total of 3608 patients were included, with 1809 in the video-assisted thoracoscopy group and 1799 in the control group. Compared with the control group, video-assisted thoracoscopy significantly reduced surgical site wound infection (odds ratio: 0.22, 95% confidence interval [CI]: 0.14-0.33, P < .001) and surgical site wound pain at postoperative day 1 (standardised mean difference [SMD]: -0.90, 95% CI: -1.17 to -0.64, P < .001) and postoperative day 3 (SMD: -1.59, 95% CI: -2.25 to -0.92, P < .001). Thus, these results showed that video-assisted thoracoscopy may have beneficial outcomes by reducing surgical site wound infection and pain. However, owing to the large variation in sample sizes and some methodological shortcomings, further validation is needed in future studies with higher quality and larger sample sizes., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Lung cancer is one of the most lethal cancers worldwide, but studies have shown that the higher the expression of programmed cell death protein 1 ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC), the more likely it will benefit from anti-PD-L1 immunotherapy. The purpose of our study was to collect and analyze abundant clinical samples in order to provide evidence for clinicians and patients who might consider anti-PD-L1 immunotherapy while jointly formulating treatment plans., Methods: On the one hand, we obtained cases from The Cancer Genome Atlas (TCGA) database, including 498 lung squamous cell cancer (LUSC) patients and 515 lung adenocarcinoma (LUAD) patients. We studied the lung caner driver gene in LUSC and LUAD. On the other hand, PD-L1 expression was detected in lung cancer tissues of 1,008 NSCLC patients with immunohistochemistry staining (IHC), and we studied the correlation between PD-L1 protein expression and clinicopathological characteristics., Results: PD-L1 expression was higher in LUSC than in LUAD at the mRNA level. In univariate analysis, PD-L1 expression at the protein level was higher in patients who were males, were LUSC, were smokers, had a tumor diameter >3 cm, had poor differentiation, or had stages III~IV disease. In multivariate analysis, PD-L1 expression was higher in patients who were LUSC or in poor differentiation., Conclusion: In term of protein level, PD-L1 expression was higher in NSCLC patients who were LUSC or in poor differentiation. We recommend that PD-L1 IHC detection can be routinely performed in such populations that are likely to benefit most from PD-L1 immunotherapy., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2023 Liu et al.)

The minichromosome maintenance (MCM) gene family comprises of ten members with key roles in eukaryotic DNA replication and are associated with the occurrence and progression of many tumors. However, whether the MCM family contributes to lung squamous cell carcinoma (LUSC) is unclear. In this study, we performed bioinformatic analysis to identify the roles of MCM genes in patients with LUSC. We also evaluated their differential gene expression, prognostic correlation, DNA methylation, functional enrichment of genetic alterations, and immunomodulation. According to the Tumor Immune Estimation Resource database, the expression of MCM2-10 mRNA was elevated in LUSC tissues. According to the Gene Expression Profiling Interactive Analysis database, MCM2-8 and MCM10 were considerably upregulated in LUSC tissues, and protein levels of all MCMs were increased in LUSC tissues. In addition, among the MCM family members, the expression of MCM3 and MCM7 showed the strongest correlation with the prognoses of patients with LUSC. To clarify the role and mechanisms of the MCM family, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment studies were performed. We detected a significant correlation between the expression patterns of MCM family members and infiltrating immune cells. In conclusion, our results improve the understanding of the aberrant expression of MCM family members in LUSC. These findings demonstrate the potential of the MCM family as therapeutic targets and biomarkers for the diagnosis and prognosis of LUSC.

Background: Distinction in the mutational profile between the common histological types, lung adenocarcinoma (LUAD) and squamous cell lung carcinoma (LUSC) has been well-established. However, comprehensive mutation profiles of the predominant histological subtypes within LUAD and LUSC remains elusive., Methods: We analyzed the mutational profile of 318 Chinese NSCLC patients of adenocarcinoma and squamous cell carcinoma predominant subtypes from seven hospitals using capture-based ultra-deep sequencing of 68 lung cancer-related genes., Results: Of the 318 NSCLC patients, 215 were diagnosed with LUAD and 103 with LUSC. Adenocarcinoma in situ and acinar adenocarcinoma were the most predominant subtypes of LUAD. On the other hand, keratinizing squamous cell carcinoma was the most predominant subtype of LUSC. Among the LUAD subtypes, EGFR sensitizing mutations were most prevalent in the invasive lepidic subtype. More than half of the patients with preinvasive adenocarcinoma in situ, minimally invasive, acinar, micropapillary and papillary subtypes were also EGFR-mutants. Patients with colloidal, invasive mucinous, and fetal subtypes had the least number of EGFR mutations. Moreover, KRAS mutations were prevalent in patients with invasive mucinous, colloid, enteric and solid subtypes. A total of 90% of the LUSC patients harbor mutations in TP53, wherein all patients except five with nonkeratinizing were TP53 mutants. PIK3CA amplifications were most prevalent in keratinizing, followed by basaloid and nonkeratinizing subtypes., Conclusion: These data suggest that the mutational profiles among the predominant histological subtypes were very distinct, which provided a reliable tool to improve treatment decisions., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

There is increasing evidence that human complement factor H‑related protein 1 (CFHR1) plays a crucial role in the development of malignant diseases. However, few studies have identified the roles of CFHR1 in the occurrence and prognosis of lung adenocarcinoma (LADC). In the present study, comprehensive bioinformatic analyses of data obtained from the Oncomine platform, UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) demonstrated that CFHR1 expression is significantly reduced in both LADC tissues and cancer cells. The patients presenting with downregulation of CFHR1 had significantly lower overall survival (OS) and post progression survival (PPS) times. Through analysis of the datasets from Gene Expression Omnibus database, we found that the compound actinomycin D promoted CFHR1 expression, further displaying the cytotoxic effect in the LADC cell line A549. In addition, the expression level of CFHR1 in the cisplatin‑resistant LADC cell line CDDP‑R (derived from H460) was also significantly reduced. Our research demonstrated that low levels of CFHR1 are specifically found in LADC samples, and CFHR1 could serve as a potential therapeutic target for this subset of lung cancers. Determination of the detailed roles of CFHR1 in LADC biology could provide insightful information for further investigations.

Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusion genes represent novel oncogenes that are associated with non-small-cell lung cancers (NSCLC). The feasibility of detecting EGFR mutations and ALK fusion genes in small biopsy specimens or surgical specimens was determined. Of the 721 NSCLC patients, a total of 305 cases were positive for EGFR mutations (42.3%). The rate of EGFR mutations in women was significantly higher than that in men. Histologically, the EGFR mutation rate in adenocarcinomas was significantly higher than that in squamous cell carcinomas. No difference in the EGFR mutation rate was observed between surgical specimens (42.1%) and small biopsy specimens (42.4%), which indicated that the EGFR mutation ratios in surgical specimens and small biopsy specimens were not different. In 385 NSCLC patients, 26 cases were positive for EML4-ALK (6.8%). However, 11.7% of the surgical specimens were EML4-ALK-positive, whereas the positive proportion in the small biopsy specimens was only 4.7%, which indicated that EML4-ALK-positive rate in the surgical specimens was significantly higher than that in the small biopsy specimens. Detection of EGFR gene mutations was feasible in small biopsy specimens, and screening for EML4-ALK expression in small biopsy specimens can be used to guide clinical treatments.

Objective: To quantitatively evaluate the evolution of the tumor perfusion in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment., Methods: To establish the preclinical transplantation model of lung adenocarcinoma, 60 BALB/c nu/nu mice was inoculated with A549 cell lines via axilla. Sixty mice were randomly divided into 2 groups. The treatment group was treated with intravenous Bevacizumab (10 mg/kg weight, in a single injection), and the control group received saline only in the same dose. Five times of volume perfusion CT (VPCT) scan was performed before treatment, and on the second, forth, sixth and tenth days of treatment, respectively. The values of blood flow (BF) in the A549 tumors were measured after scanning. The microvessel density (MVD), vessel maturity index (VMI) in the tumors were determined using multiplexed QDs-based immunohistochemical staining., Results: Comparing the values of BF, VMI and MVD between the two groups on the same day before treatment, the values of BF, VMI and MVD of the treatment group were (13.5±1.5) ml·(100 ml)(-1)·min(-1,) 0.14±0.04, (45.7±16.5)/HPF, respectively, and those in the control group were (13.4±1.6) ml·(100 ml)(-1)·min(-1) , 0.14±0.05, (48.0±7.0) /HPF , respectively. There was no significant difference between the two groups (all P>0.05). And on the second, forth, sixth, tenth days of treatment, the values of BF of the treatment group were (17.9±7.3), (32.2±6.9), (18.5±2.4) and (13.8±1.8) ml·(100 ml)(-1)·min(-1,) respectively, and those in the control group were (10.5±0.6), (9.6±0.8), (5.7±1.2) and (1.9±1.0) ml·(100 ml)(-1)·min(-1,) respectively. The values of VMI of the treatment group were 1.17±0.22, 3.25±0.23, 2.94±0.31 and 1.07±0.18, respectively, and those in the control group were 0.12±0.03, 0.13±0.03, 0.15±0.03, and 0.13±0.03, respectively. The values of MVD of the treatment group were (38.0±6.3), (24.3±5.4), (15.2±3.4) and (13.5±4.7)/HPF, respectively, and those in the control group were (44.8±5.9), (48.0±12.8), (41.8±5.7) and (45.7±20.3)/HPF, respectively. In treated mice, BF and VMI were significantly higher than those in the control group (all P<0.01). BF and VMI increased from day2, and reached the peak at day4 (P<0.01), then decreased at day6, however the value of BF at day6 was still higher than that in the baseline (P<0.01) and decreased to the baseline level at day10; while the value of VMI was still higher than that in the baseline at day10. And on the forth, sixth, tenth days of treatment, in treated mice, the values of MVD were significantly lower than those in the control group and the baseline level before treatment (all P<0.01). In control mice, BF decreased (all P<0.01) with the time, while MVD and VMI had no changes., Conclusions: The tumor perfusion and vessel maturity are transiently increased in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment. VPCT is helpful to quantify the evolution of the tumor perfusion and then evaluate the functional changes of tumor vessel maturity.

Lung cancer as an aggressive type tumor is rapidly growing and has become the leading cause of cancer-related death worldwide. γ-Glutamylcyclotransferase (GGCT) has been shown as a diagnostic marker in various cancers. To reveal whether there is a correlation between GGCT and lung cancer, GGCT expression in human lung cancer cell lines was first determined by real-time quantitative PCR and western blot. GGCT is expressed in all tested lung cancer cell lines, A549, H1299, and H460. Then, a lentivirus-based system was applied to knock down GGCT in A549 cells, which were thus divided into Lv-shGGCT, Lv-shCon, and Con (noninfected) groups. Methylthiazol tetrazolium assay showed that the cell proliferation was decreased by over 50% in the Lv-shGGCT group compared with controls. The size and number of colonies were dramatically reduced in the GGCT knockdown group, as measured by colony formation assay. Moreover, A549 cells infected with Lv-shGGCT were arrested in the G0/G1 phase as assayed by flow cytometry. Furthermore, the expression levels of CDK4, CDK6, and cyclin D1 were decreased and the cleaved level of PARP was increased in GGCT knockdown cells. In conclusion, GGCT plays a critical role in lung cancer cell proliferation and may be a potential cancer therapeutic target.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of vessels, particularly within capillaries, with exception of larger arteries and veins. The authors reported a case of a 45-year-old woman who was admitted in hospital with refractory fever, cough and progressive dyspnea despite of receiving broad-spectrum antibiotics. Computed tomography (CT) of the lung showed bilateral patchy ground-glass opacities with some pleural effusion in the left lung. A CT-guided percutaneous lung biopsy was performed and primary pulmonary intravascular large B-cell lymphoma was diagnosed by histopathology, immunophenotype and fluorescence in situ hybridization. The patient's general status was improved after chemotherapy with R-CHOP. CT-guided percutaneous biopsy of lung is a safe and accurate diagnostic procedure in IVLBCL.

Insulin-like growth factor binding protein 2 (IGFBP2) is involved in the progression of many epithelial cancers. However, its role in non-small cell lung cancer (NSCLC), another type of epithelial cancer, remains unclear. We detected IGFBP2 expression using immunohistochemistry in surgically resected tumors from 110 NSCLC patients, 37 of which had metastases. The positive rate of IGFBP2 expression was compared between the metastatic and the non-metastatic group, and correlations of IGFBP2 expression with metastasis and overall survival were analyzed. We also investigated the expression of IGFBP2 in microvesicles (MVs) collected from primary lung cancer cell cultures, and in different locations of newly resected NSCLC tumors, using immunoblotting. The overall positive rate of IGFBP2 expression in lung cancer was 51.8 % and it was significantly higher in the metastatic group than in the non-metastatic group (70.3 and 42.5 % respectively, p < 0.01). And the higher the lymph node stage, the higher the positive rate. Cytoplasmic expression was predominant in the majority of the tumors. Based on multivariate regression analysis, IGFBP2 was correlated with metastasis and poor overall survival (Hazard ratio: 3.56 and 3.23 respectively). IGFBP2 was detectable in the MVs collected from IGFBP2 positive cell lines, and its expression was most abundant in the marginal region of the newly resected tumors. IGFBP2 is associated with metastasis and poor survival of lung cancer. Its presence in MVs and high abundance in the marginal region of tumors suggest that its association with metastasis may be related to tumor microenviroment remodeling in NSCLC.

Background: Benign metastasizing leiomyoma (BML) occurs in a low proportion of uterine leiomyomas and treatment methods for BML are diverse and controversial. The study introduces preliminary experiences in the diagnosis and treatment of BML with the purpose of finding a suitable management strategy for these patients., Methods: Three patients with BML were treated in our department from April 2008 to July 2012. Each of these patients presented with multiple nodules in both lungs, where we performed video-assisted thoracoscopic wedge resection to harvest enough tissue for histopathologic and immunohistochemical examination. The patients were treated with medical castration or surgical castration after the diagnosis of BML., Results: The ultimate pathologic results ruled out the possibility of leiomyosarcoma and other metastatic diseases, and confirmed that the pulmonary lesions were BML. The lung lesions remained stable in two patients who were treated by surgical castration, and the lung nodules regressed in one patient treated with gonadotropin-releasing hormone analogues., Conclusions: The diagnosis of BML is based on the medical history of uterine myomas and histopathologic and immunohistochemical examination of lung nodules. Video-assisted thoracoscopic wedge resection is the best way to harvest tissue for diagnosis. The better outcomes in BML seem to call for medical intervention, either chemical or surgical, after diagnosis is made.

Notch receptor signaling pathway (NRSP) is increasingly linked to carcinogenesis. Non-small cell lung cancer (NSCLC) appears to actively utilize this conserved developmental pathway. The aims of this study are to determine whether or not Notch 1-4 are overexpressed in NSCLC tissues compared with normal lung tissues and whether inhibiting NRSP could induce caspase-dependent or caspase-independent apoptosis. Immunohistochemistry was used to evaluate the expression of Notch 1-4 in 101 NSCLC tissue samples and 30 normal lung tissue samples. DAPT was used to repress NRSP in SK-MES-1 cells. Apoptosis was determined by Annexin V and PI staining. Cleaved poly ADP-ribose polymerase (PARP) was measured by Western blot; X-linked inhibitor of apoptosis protein (XIAP) and Survivin were assessed by qRT-PCR and Western blot; the release of second mitochondria-derived activator of caspase (Smac) from mitochondria to cytoplasm was evaluated by Western blot; the subcellular locations of endonuclease G (Endo G) and apoptosis inducing factor (AIF) were observed by Western blot and indirect immunofluorescence analysis. (Mech Dev, 98, 2000, 95) Notch 1-4 are up-regulated in NSCLC tissues and Notch 1, 2 are positively correlated with lymph node metastasis, (Proc Natl Acad Sci U S A, 106, 2009, 22293) DAPT treatment could inhibit NRSP and induce apoptosis, with a marked increase in cleaved PARP, decreases in XIAP and Survivin proteins and concomitant release of Smac, EndoG, and AIF from mitochondria, indicating that inhibiting NRSP by DAPT triggers caspase-dependent and caspase-independent apoptosis., (© 2012 The Authors. APMIS © 2012 APMIS.)

Objective: To explore the degree, mechanism and clinical significance of three-dimensional tumor microvascular architecture phenotype heterogeneity (3D-TMAPH) in non-small cell carcinoma (NSCLC)., Methods: Twenty-one samples of solitary pulmonary nodules were collected integrally. To establish two-dimensional tumor microvascular architecture phenotype (2D-TMAP) and three-dimensional tumor microvascular architecture phenotype (3D-TMAP), five layers of each nodule were selected and embedded in paraffin. Test indices included the expressions of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), EphB4, ephfinB2 and microvascular density marked by anti-CD34 (CD34-MVD). The degrees of 3D-TMAPH were evaluated by the coefficient of variation and extend of heterogeneity. Spearman rank correlation analysis was used to investigate the relationships between 2D-TMAP, 3D-TMAP and clinicopathological features., Results: 3D-TMAPH showed that 2D-TMAP heterogeneity was expressed in the tissues of NSCLC. The heterogeneities in the malignant nodules were significantly higher than those in the active inflammatory nodules and tubercular nodules. In addition, different degrees of heterogeneity of CD34-MVD and PCNA were found in NSCLC tissues. The coefficients of variation of CD34- MVD and PCNA were positively related to the degree of differentiation (all P<0.05), but not related to the P-TNM stages, histological type or lymphatic metastasis (all P>0.05). The level of heterogeneity of various expression indexes (ephrinB2, EphB4, VEGF) in NSCLC tissues were inconsistent, but there were no significant differences in heterogeneity in NSCLC tissues with different histological types (P>0.05)., Conclusion: 3D-TMAPH exists widely in the microenvironment during the genesis and development of NSCLC and has a significant impact on its biological complexity.

ADAM23, a member of a disintegrin and metalloprotease (ADAM) family, has been reported to be expressed in several types of tumours. The exact role of ADAM23 and the possible mechanisms in which it is involved in non-small-cell lung carcinoma (NSCLC) remains unclear. Therefore, this study was designed to explore the expression of ADAM23 and its correlation with promoter methylation in NSCLC. Immunohistochemistry and RT-PCR together with Western blotting methods were used to analyse the expression of ADAM23 in 52 cancer tissue samples and eight benign pulmonary lesions as well as four cell lines. The methylated status of ADAM23 gene was determined with methylation-specific PCR (MSP). The results of immunohistochemistry showed that the expression of ADAM23 protein was lower in NSCLC than that in corresponding normal tissues and benign pulmonary lesions (38.5%vs. 86.5% and 87.5%, P < 0.05), and decreased as NSCLC progressed. Meanwhile, methylation of ADAM23 gene was observed in 21 of 52 NSCLC tissues (40.4%), much higher than that of adjacent normal tissues (7.6%) and benign pulmonary lesions (0/8). In the cancer tissues of ADAM23-negative samples, the rate of ADAM23 gene methylation was 50.3% (17/32). ADAM23 expression and its promoter methylation were negatively associated (r = -0.328, P = 0.017). Moreover, weak expression of ADAM23 in methylated cancer cells increased after treatment with 5-aza-2'-deoxycytidine (5-Aza-2'-dC), confirming that methylation was responsible for the gene downregulation. Our results demonstrate that the expression level of ADAM23 is likely to be involved in the progression of NSCLC and its downregulation is probably correlated with promoter methylation. These findings may provide potential diagnostic and prognostic information about NSCLC., (© 2011 The Authors. International Journal of Experimental Pathology © 2011 International Journal of Experimental Pathology.)

Background: Peripheral subpleural solitary pulmonary nodules can be visualized and resected easily at thoracoscopy, but it is very difficult to localize deep nonpalpable pulmonary nodules that lie in lung parenchyma. The purpose of this article was to study the effectiveness of video-assisted thoracoscopic solitary pulmonary nodules resection after computed tomography (CT)-guided hookwire localization and to review the literature related to solitary pulmonary nodule diagnosis and treatment., Methods: From April 2008 to June 2009, 43 patients with a solitary pulmonary nodule who had undergone CT-guided hookwire localization and video-assisted thoracoscopic surgery (VATS) were studied., Results: Two cases were considered unsuccessful, other patients underwent CT-guided hookwire localization successfully, and ten patients had an asymptomatic minimal pneumothorax that did not require any intervention. The diameter of nodules ranged from 5 to 30 mm as measured by CT (mean 17.2±7.5 mm). The distance between the center of nodule and visceral pleural ranged from 2 to 40 mm (mean 18.5±9.3 mm). Of the 41 scheduled VATS procedures, 38 patients underwent thoracoscopic wedge resection. Twenty-two of 41 patients who revealed primary lung cancer after frozen-section examination underwent VATS lobectomy and lymphadenectomy. Three patients were converted to thoracotomy, and a major postoperative hemothorax occurred in one patient. No intra- or postoperative mortality or morbidity was recorded., Conclusions: Video-assisted thoracoscopic solitary pulmonary nodule resection after CT-guided hookwire localization is a safe and effective procedure for accurate diagnosis and resection of indeterminate solitary pulmonary nodules.

Background: Whether tumor size and stage distribution are correlated remains controversial. The objective is to assess the relationship between tumor size and disease stage distribution in non-small cell lung cancer (NSCLC)., Methods: We conducted a retrospective analysis of 917 cases of NSCLC that were resected in the Cancer Hospital of Fudan University and Shanghai Sixth Hospital between January 2000 and February 2009. Tumor sizes were grouped into five categories: ≤20 mm, 21 to 30 mm, 31 to 50 mm, 51 to 70 mm and ≥71 mm., Results: Age and tumor size affected stage distribution: patients 60 years or older had a higher percentage of N0M0 disease than patients younger than 60 years (61.67% vs. 44.85%, p < 0.01). The smaller the tumor, the more likely the disease was N0M0 status (p < 0.05). For tumors ≤20 mm in diameter, the proportion of cases with N0M0 status was 70.79%, compared to 58.88% for 21 to 30 mm, 48.03% for 31 to 50 mm, 47.55% for 51 to 70 mm, 33.33% for ≥71 mm. The mean (± SD) tumor size of cases with N0M0 status was 37.17 ± 21.34 mm, compared to 45.75 ± 23.19 mm for cases with other status., Conclusions: There is a statistically significant relationship between tumor size and distribution of disease stage of primary NSCLC tumors: the smaller the tumor, the more likely the disease is N0M0 status.

Background and Objective: It has been proven that endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was a new minimally invasive method in the diagnosis for mediastinal lymph nodes. The aim of this study is to evaluate the diagnostic and staging yield of EBUS-TBNA for lung cancer., Methods: Seventy-five patients with tumors and enlarged mediastinal lymph nodes found by CT underwent the diagnosis by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) from April 1, 2009 to Febuary 8, 2010. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of EBUS-TBNA were evaluated., Results: Seventy-five patients with 177 lymph node groups (2.4 groups in average) were studied. Histopathological samples were found in 49.33% patients and in 28.81% groups. Overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of EBUS-TBNA for diagnostic were 98.43%, 100.00%, 100.00%, 91.67% and 98.66%, respectively, in per patient analysis and were 95.10%, 100%, 100.00%, 82.93%, and 96.05%, respectively, in per group analysis, higher than CT examination (P < 0.05) expect for sensitivity (P = 0.435). Staging changed in 19 (26.03%) patients after EBUS-TBNA., Conclusion: EBUS-TBNA proved to be a safe procedure with a high yield for the diagnosis of lung cancer.

Objective: To investigate the expression of fibroblast growth factor-2 (FGF-2) and osteopontin (OPN) in non-small cell lung cancer (NSCLC) tissues and analyze the correlation between FGF-2 and OPN., Methods: Immunohistochemical SP method was used to detect the expression of FGF-2 and OPN in 76 patients with NSCLC and 15 normal lung tissues. The effect of FGF-2 on OPN expression at mRNA and protein level in A549 cell was examined by RT-PCR and Western blot., Results: The positive expression of FGF-2 (65.8%) and OPN (60.5%) in the NSCLC tissues was significantly higher than that in the normal lung tissues (13.3% and 0, respectively ) (P<0.01). The expression of FGF-2 and OPN was closely related to TNM stages and the lymph node metastasis (all Ps<0.01), but not to histological types, sex, and age of NSCLC patients (all Ps>0.05).A positive correlation was found between the expression of FGF-2 and OPN in NSCLC (r=0.552,P<0.01). The expression of OPN protein and mRNA was up-regulated by FGF-2 in A549 cells., Conclusion: The overexpression of FGF-2 and OPN is related to the metastasis and invasion of NSCLC.FGF-2 may promote the metastasis and invasion of NSCLC depending on the upregulation of OPN expression.

Lung cancer is the leading cause of cancer death. The prognosis of metastatic lung cancer is poor. We had previously established the condition to expand human gammadelta T-cells in peripheral blood and tumor infiltrating T lymphocytes with immobilized anti-TCRgammadelta antibody. Such expanded gammadelta T-cells exhibited potent cytolytic activity to different tumor cell lines in vitro and in vivo. Here we further characterized human anti-TCRgammadelta-expanded gammadelta T-cells and tested their antitumor function in treatment for lung cancer in nude mice. In comparison to gammadelta T-cells activated by phosphoantigen, a prevalent Vdelta2 stimulus, anti-TCRgammadelta-expanded gammadelta T-cells had similar major subset with Vdelta2 phenotype, but they had about 10% of Vdelta1 subsets and high percentages of CD27(-)CD45RA(-) and CD27(-)CD45RA(+) effector cells. They also displayed TCR diversity of multiple clones. Importantly, the antibody-expanded gammadelta T-cells showed strong cytotoxicity to three lung cancer cell lines and had significant antitumor effect on squamous lung carcinoma in nude mice. The ex vivo anti-TCRgammadelta-expanded gammadelta T-cells prolonged tumor bearing mouse survival and slowed down tumor growth, with similar efficacy to chemotherapy by cis-platinum. Moreover, adoptively transferred human gammadelta T-cells survived for more than one month in vivo. Finally, gammadelta T-cells derived from 11 cases of patients with lung cancer had proliferative activity after TCRgammadelta ligandation, displayed marked cytotoxicity to lung cancer cells and expressed cytotoxicity- or antitumor activity-related molecules, such as perforin, granzyme A and B, Fas ligand, TNFalpha and IFNgamma. Taken together, our finding suggests that anti-TCRgammadelta expanded gammadelta T-cells may be used as cellular therapy in treatment of lung cancer.

Objective: To investigate the relation between expression of vascular endothelial growth factor (VEGF)/ proliferating cell nuclear antigen (PCNA) and multi-slice spiral computer tomography (MSCT) perfusion imaging., Methods: Sixty-one patients who underwent CT perfusion scan by 16-slice spiral CT were examined. Among them,22 were brought into our research after surgery. The corresponding layers of tumor tissue specimens to the layer of CT perfusion scan were selected to determine the expression of CD34,VEGF, and PCNA. Spearman correlation analysis was used to determine the relation between differentiation of non-small cell lung cancer (NSCLC), the expression of CD34,VEGF/PCNA, and CT perfusion parameters., Results: There was a lot of heterogeneity in VEGF and PCNA expression of NSCLC.The degree of differentiation had positive correlation with the uncomplete lumen of the surrounding area CD34-MVD and the expression of PCNA and VEGF (P<0.05).There were positive correlations between the uncomplete lumen of the surrounding area CD34-MVD and expression of VEGF and PCNA, respectively (both P<0.05). Blood flow (BF), blood volume (BV),and peak enhancement image (PEI) decreased with the decreasing differentiation of NSCLC (P<0.05). The total CD34-MVD showed a positive correlation with PEI (P<0.05),and the uncomplete lumen of the surrounding area CD34-MVD showed a negative correlation with BF,BV, and PEI (all P<0.05). The PCNA expression showed a negative correlation with BF,BV, and PEI (P<0.05)., Conclusion: PCNA and VEGF expression in NSCLC regulates angiogenesis and proliferation at the same time. Perfusion parameters reflect the expression of microvascular architecture phenotype, and exactly evaluate the malignant degree of tumor.

To investigate the mechanism by which fibroblast growth factor 2 (FGF-2) inhibits apoptosis in the human small cell lung cancer cell line H446 subjected to serum starvation, apoptosis was evaluated by flow cytometry, Hoechst 33258 staining, caspase-3 activity, and DNA fragmentation. Survivin expression induced by FGF-2 and protein kinase C alpha (PKC alpha) translocation was detected by subcellular fractionation and Western blot analysis. In addition, FGF-2-induced release of Smac from mitochondria to the cytoplasm was analyzed by Western blotting and immunofluorescence. FGF-2 reduced apoptosis induced by serum starvation and up-regulated survivin expression in H446 cells in a dose-dependent and time-dependent manner, and inhibited caspase-3 activity. FGF-2 also inhibited the release of Smac from mitochondria to the cytoplasm induced by serum starvation and increased PKC alpha translocation from the cytoplasm to the cell membrane. In addition, PKC inhibitor inhibited the expression of survivin. FGF-2 up-regulates the expression of survivin protein in H446 cells and blocks the release of Smac from mitochondria to the cytoplasm. PKC alpha regulated FGF-2-induced survivin expression. Thus, survivin, Smac, and PKC alpha might play important roles in the inhibition of apoptosis by FGF-2 in human small cell lung cancer cells.