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Lung Cancer

Lung cancer is one of the most common types of cancer. The lungs are a pair of cone-shaped organs situated inside the chest, they bring oxygen into the body and take out waste carbon dioxide. There is a strong link between smoking and lung cancer. There are two main categories of lung cancer; Small Cell Lung Cancer (SCLC) , and Non-Small Cell Lung Cancer (NSCLC). World-wide over 1 million people are diagnosed with lung cancer each year.

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Non-Small Cell Lung Cancer
Small Cell Lung Cancer
Risk Factors and Prevention of Lung Cancer
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Information Patients and the Public (19 links)


Information for Health Professionals / Researchers (17 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Lee WH, Loo CY, Ong HX, et al.
Synthesis and Characterization of Inhalable Flavonoid Nanoparticle for Lung Cancer Cell Targeting.
J Biomed Nanotechnol. 2016; 12(2):371-86 [PubMed] Related Publications
Current cancer treatments are not adequate to cure cancer disease, as most chemotherapeutic drugs do not differentiate between cancerous and non-cancerous cells; which lead to systemic toxicity and adverse effects. We have developed a promising approach to deliver a potential anti-cancer compound (curcumin) for lung cancer treatment through pulmonary delivery. Three different sizes of curcumin micellar nanoparticles (Cur-NPs) were fabricated and their cytotoxicity effects (proliferation, apoptosis, cell cycle progression) were evaluated against non-small-cell lung cancer, human lung carcinoma (A549) and human lung adenocarcinoma (Calu-3). The in vitro cytotoxicity assay showed that Cur-NPs were more effective to kill lung cancer cells compared to DMSO-solubilised raw curcumin. The potency of the anti-cancer killing activities was size-dependent. Both raw curcumin and Cur-NPs were not toxic to healthy lung cells (BEAS-2B). Smaller Cur-NPs accumulated within nucleus, membrane and cytoplasm. Cur-NPs also induced apoptosis and caused G2/M arrest in both A549 and Calu-3 cell lines. Compared to raw curcumin, Cur-NPs were more effective in suppressing the expression of the inflammatory marker, Interleukin-8 (IL8). The aerosol performance of Cur-NPs was characterized using the next generation impactor (NGI). All Cur-NPs showed promising aerosolization property with mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) ranging between 4.8-5.2 and 2.0-2.1, respectively. This study suggests that inhaled curcumin nanoparticles could potentially be used for lung cancer treatment with minimal side effects.

Jiang LY, Bi R, Ding FB, et al.
Prognostic significance of overexpressed matrix metalloproteinase-2, mouse-double minute: 2 homolog and epidermal growth factor receptor in non-small cell lung cancer.
J BUON. 2016 Mar-Apr; 21(2):341-8 [PubMed] Related Publications
PURPOSE: To evaluate the rate of overexpression of matrix metalloproteinase-2 (MMP2), mouse double minute 2 homolog (MDM2) and epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC), and evaluate their correlation with clinicopathological parameters and prognosis.
METHODS: This was a prospective cohort study conducted from 2003 to 2008 among 184 NSCLC patients who underwent tumor resection. Each patient's clinical history and tumor characteristics were obtained from histopathology reports and medical records. EGFR, MDM2 and MMP2 expression were assessed by immunohistochemical (IHC) staining of the tissue specimens.
RESULTS: MDM2 overexpression was observed in 70 (38%) of the patients studied, and was significantly higher in younger patients (p=0.01). Only 46 (25%) of patients had overexpression of MMP2. EGFR positive staining occurred in 105 (57%percnt;) of the evaluated tumor specimens and was more frequent in specimens with squamous cell carcinoma (p<0.001), the elderly (p<0.001), and in smokers (p<0.001). Independent risk factors for mortality were older age (adjusted odds ratio/aOR 1.3=), being a smoker (aOR 10), having stage II disease (aOR 10.8) or stage III/IV disease (aOR 28.3), expression of EGFR (aOR 5.9) and MMP2 (aOR 4.1). However, the expression of MDM2 independently predicted a reduced risk of death (aOR 0.3).
CONCLUSION: Overexpression of MMP2 and EGFR were independent risk factors for mortality in NSCLC patients, while overexpression of MDM2 independently predicted a reduced risk of death.

Imai H, Murakami H, Yoshino R, et al.
Comparison of the efficacy of radiotherapy between postoperative mediastinal lymph node recurrence and stage III disease in non-small cell lung cancer patients.
J BUON. 2016 Mar-Apr; 21(2):333-40 [PubMed] Related Publications
PURPOSE: It is unknown if local treatment is equally effective in non-small cell lung cancer (NSCLC) patients with postoperative mediastinal lymph node recurrence or primary stage III disease. The purpose of this study was to investigate the effectiveness of radiotherapy, with or without chemotherapy, in patients with postoperative mediastinal lymph node recurrence.
METHODS: Patient characteristics, treatment response and survival were compared between NSCLC patients with mediastinal lymph node metastases treated between 2002-2009 by radiotherapy alone or by chemoradiotherapy (group A, N=33) and those with primary stage III disease (group B, N = 157).
RESULTS: Men accounted for 60.6% of group A and 78.9% of group B (p=0.04 patients). ECOG performance status 0 was detected in 78.7% of group A and 57.3% of group B (p=0.02). The response rates in groups A and B were 66.6 and 72.3%, respectively (p=0.64). Progression-free survival (PFS) was similar between groups A and B (median 15.0 vs 11.0 months; hazard ratio [HR] 0.78; 95% CI 0.51-1.20; p=0.26). However, overall survival (OS) was better in group A than in group B (median 67.0 vs 39.0 months; HR 0.56; 95% CI 0.29-0.97; p=0.03). Postoperative PFS (median 12.5 vs 19.0 months; HR 1.50; 95% CI 0.64-3.49; p=0.34) and OS (median, 67.0 vs 60.0 months; HR 1.22; 95% CI 0.36-4.14; p=0.74) were similar between the group A treatments (radiotherapy and chemoradiotherapy, respectively).
CONCLUSION: Postoperative mediastinal lymph node recurrent NSCLC demonstrated distinctive features including better OS compared to patients with primary stage III disease, despite similar response rates and PFS.

Zhao Z, Su Z, Zhang W, et al.
A randomized study comparing the effectiveness of microwave ablation radioimmunotherapy and postoperative adjuvant chemoradiation in the treatment of non-small cell lung cancer.
J BUON. 2016 Mar-Apr; 21(2):326-32 [PubMed] Related Publications
PURPOSE: To evaluate the differences in the outcomes of patients with stage II and IIIa non-small cell lung cancer (NSCLC) treated with either 131I-labeled mouse/human chimeric monoclonal antibody against intracellular DNA exposed in necrotic and degenerating regions of tumors (131I-chTNT-mediated radioimmunotherapy) combined with percutaneous microwave coagulation therapy (PMCT) guided by computed tomography (CT) or with postoperative adjuvant chemoradiation.
METHODS: Ninety-six patients with stage II and IIIa NSCLC were randomized into two groups. Group A included 49 patients who were treated with chemotherapy with docetaxel and cisplatin and three-dimensional conformal radiotherapy 3-4 weeks after surgery. Group B included 47 patients treated with 131I-chTNT and PMCT sequentially, with follow-up chemotherapy.
RESULTS: The survival rates of patients in group A for the first and second years were 79.59% and 48.98%, respectively. The median survival was 23.0 months. Survival rates at 1 and 2 years for group B were 82.98% and 53.19%, respectively and the median survival was 29.1 months. The survival rate of group B patients for the first and second years was better compared with group A, and the difference in median survival between the groups was statistically significant (p<0.05). However, median survival and the incidence of adverse events were not significantly different between the two groups.
CONCLUSIONS: 131I-chTNT radioimmunotherapy with PMCT has a complementary effect in NSCLC, which can effectively improve therapeutic ratio and survival of patients effectively and has the same effect as that of post-operative adjuvant chemoradiation.

Xu H, Ma J, Zheng J, et al.
MiR-31 Functions as a Tumor Suppressor in Lung Adenocarcinoma Mainly by Targeting HuR.
Clin Lab. 2016; 62(4):711-8 [PubMed] Related Publications
BACKGROUND: Gene expression is widely regulated by miRNAs and RNA binding proteins. In this study, we mainly focused on miR-31 and a RNA binding protein, HuR (Hu antigen R).
METHODS: The levels of miR-31 and HuR in lung carcinoma cells and lung cancer tissues were explored using RT-qPCR and western blot, respectively. Luciferase reporter assay was used to determine the target gene of miR-31. Cell apoptosis and migration were studied using flow cytometry and the transwell invasion assay. The down-stream genes of HuR were explored with western blot assay.
RESULTS: miR-31 was decreased in lung carcinoma cells and lung cancer tissues, while the protein level of HuR was increased. HuR was the target gene of miR-31. Inhibition of miR-31 and overexpression of HuR resulted in the upregulation of cyclins A2, B1, D1 and VEGF (vascular endothelial growth factor). Furthermore, overexpression of miR-31 prompted lung cancer cell apoptosis and inhibited cell migration.
CONCLUSIONS: Reduction of miR-31 expression enhanced lung cancer proliferation and migration by repressing HuR expression.

Gao J, Wu H, Shi X, et al.
Comparison of Next-Generation Sequencing, Quantitative PCR, and Sanger Sequencing for Mutation Profiling of EGFR, KRAS, PIK3CA and BRAF in Clinical Lung Tumors.
Clin Lab. 2016; 62(4):689-96 [PubMed] Related Publications
BACKGROUND: The clinical application of next-generation sequencing technologies has offered a more comprehensive understanding of the mutational profile of tumor samples. The study was aimed to evaluate the feasibility of the NextDaySeq-Lung panel, which is an NGS-based assay for mutation analysis of key driver genes in lung cancer, in a clinical setting.
METHODS: A total of 138 FFPE samples of non-small cell lung cancer (NSCLC) were examined in parallel with assays developed on the next-generation sequencing (NGS), quantitative PCR (QPCR), and Sanger sequencing (Sanger) platforms for somatic mutations in EGFR, KRAS, PIK3CA, and BRAF. The assays with the three platforms were compared and analyzed.
RESULTS: Compared with Sanger, NGS and QPCR assays have significant higher sensitivity, as Sanger failed to detect variants with mutation rates lower than 15%. Meanwhile, NGS and QPCR assays showed similar analytical sensitivity, specificity, and high concordance. In addition, the NGS assay exhibited advantages over QPCR in providing accurate information of allele sequence and mutation frequency, and detecting non-hotspot mutations.
CONCLUSIONS: We reported the validation of NextDaySeq-Lung panel for mutation analysis in the clinical samples of lung cancer. The NGS assay has significant technical advantages over Sanger and QPCR assays. It shows good potential as a solid molecular diagnostics assay in the clinical setting.

Wang BZ, Yu ZG
The combination use of 1-O-acetylbritannilactone (ABL) and gemcitabine inhibits cell growth and induces cell apoptosis in lung adenocarcinoma cells.
Pharmazie. 2016; 71(4):213-7 [PubMed] Related Publications
1-O-acetylbritannilactone (ABL), a natural chemical component obtained from Chinese traditional medicine, Inula britannica, has been demonstrated to have anticancer activities. In the present study, we evaluated the anti-proliferative and the pro-apoptotic abilities of ABL alone or in combination with gemcitabine in human NSCLC cell line. A549 cells were treated, in vitro, with ABL, gemcitabine, and the combination of ABL and gemcitabine for 72 h. Our results showed ABL and gemcitabine inhibited cell growth and induced apoptosis of A549 cells. These effects after the combination of ABL and gemcitabine were superior to those of each alone. Furthermore, signal transduction analysis revealed NF-κB expression was significantly decreased by ABL and the combination treatment. IκBα and Bax levels were up regulated whereas Bcl-2 was substantially downregulated after all treatments. Our findings suggest that ABL combined with gemcitabine elicits a potent apoptosis of lung cancer cell and hence ABL has the potential to be developed as a chemotherapeutic agent.

Katki HA, Kovalchik SA, Berg CD, et al.
Development and Validation of Risk Models to Select Ever-Smokers for CT Lung Cancer Screening.
JAMA. 2016; 315(21):2300-11 [PubMed] Free Access to Full Article Related Publications
IMPORTANCE: The US Preventive Services Task Force (USPSTF) recommends computed tomography (CT) lung cancer screening for ever-smokers aged 55 to 80 years who have smoked at least 30 pack-years with no more than 15 years since quitting. However, selecting ever-smokers for screening using individualized lung cancer risk calculations may be more effective and efficient than current USPSTF recommendations.
OBJECTIVE: Comparison of modeled outcomes from risk-based CT lung-screening strategies vs USPSTF recommendations.
DESIGN, SETTING, AND PARTICIPANTS: Empirical risk models for lung cancer incidence and death in the absence of CT screening using data on ever-smokers from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; 1993-2009) control group. Covariates included age; education; sex; race; smoking intensity, duration, and quit-years; body mass index; family history of lung cancer; and self-reported emphysema. Model validation in the chest radiography groups of the PLCO and the National Lung Screening Trial (NLST; 2002-2009), with additional validation of the death model in the National Health Interview Survey (NHIS; 1997-2001), a representative sample of the United States. Models were applied to US ever-smokers aged 50 to 80 years (NHIS 2010-2012) to estimate outcomes of risk-based selection for CT lung screening, assuming screening for all ever-smokers, yield the percent changes in lung cancer detection and death observed in the NLST.
EXPOSURES: Annual CT lung screening for 3 years beginning at age 50 years.
MAIN OUTCOMES AND MEASURES: For model validity: calibration (number of model-predicted cases divided by number of observed cases [estimated/observed]) and discrimination (area under curve [AUC]). For modeled screening outcomes: estimated number of screen-avertable lung cancer deaths and estimated screening effectiveness (number needed to screen [NNS] to prevent 1 lung cancer death).
RESULTS: Lung cancer incidence and death risk models were well calibrated in PLCO and NLST. The lung cancer death model calibrated and discriminated well for US ever-smokers aged 50 to 80 years (NHIS 1997-2001: estimated/observed = 0.94 [95%CI, 0.84-1.05]; AUC, 0.78 [95%CI, 0.76-0.80]). Under USPSTF recommendations, the models estimated 9.0 million US ever-smokers would qualify for lung cancer screening and 46,488 (95% CI, 43,924-49,053) lung cancer deaths were estimated as screen-avertable over 5 years (estimated NNS, 194 [95% CI, 187-201]). In contrast, risk-based selection screening of the same number of ever-smokers (9.0 million) at highest 5-year lung cancer risk (≥1.9%) was estimated to avert 20% more deaths (55,717 [95% CI, 53,033-58,400]) and was estimated to reduce the estimated NNS by 17% (NNS, 162 [95% CI, 157-166]).
CONCLUSIONS AND RELEVANCE: Among a cohort of US ever-smokers aged 50 to 80 years, application of a risk-based model for CT screening for lung cancer compared with a model based on USPSTF recommendations was estimated to be associated with a greater number of lung cancer deaths prevented over 5 years, along with a lower NNS to prevent 1 lung cancer death.

Huesch MD, Ong MK
Lung Cancer Care Before and After Medicare Eligibility.
Inquiry. 2016; 53 [PubMed] Related Publications
Uninsured and underinsured near-elderly may not have timely investigation, diagnosis, or care of cancer. Prior studies suggest Medicare eligibility confers significant and substantial reductions in mortality and increases in health service utilization. We compared 2245 patients diagnosed with lung cancer at ages 64.5 to 65 years and 2512 patients aged 65 to 65.5 years, with 2492 patients aged 65.5 to 66 years (controls) in 2000 to 2005. Compared with controls, patients diagnosed with lung cancer before Medicare eligibility had no statistically significant differences in cancer stage, time to treatment, type of treatment, and survival. Study power was sufficient to exclude mortality reductions and health service utilization changes of the magnitude found in prior work, suggesting that typically, appropriate lung cancer care may be sought and delivered regardless of insurance status.

Mohapatra PR, Aggarwal D, Punia RS, Janmeja AK
Adenocarcinoma of Lung Presenting as Interstitial Lung Disease.
Indian J Chest Dis Allied Sci. 2015 Oct-Dec; 57(4):239-41 [PubMed] Related Publications
Interstitial lung diseases (ILDs) presenting as lung cancer have been reported rarely from India. The present case describes a possibly primary lung cancer in a non-smoker who presented radiologically as a case of ILD. The possible mechanisms available in the literature are discussed.

Agarwal S, Gupta K, Mullick S, et al.
Pulmonary Tumourlets: Case Report and Review of Literature.
Indian J Chest Dis Allied Sci. 2015 Oct-Dec; 57(4):235-8 [PubMed] Related Publications
We report a case of tumourlets of the lung associated with carcinoid and neuroendocrine cell hyperplasia, found incidentally in a 30-year-old woman, who underwent bullectomy for pneumothorax. These lesions are histologically similar to carcinoid, but differ in molecular pathogenesis about which little is known. Their nature and significance is debated. Here, we point out the importance of histological, clinical, and diagnostic aspects and follow-up to have evidence of eventual malignant evolution.

Wang TL, Song YQ, Ren YW, et al.
Dual Specificity Phosphatase 6 (DUSP6) Polymorphism Predicts Prognosis of Inoperable Non-Small Cell Lung Cancer after Chemoradiotherapy.
Clin Lab. 2016; 62(3):301-10 [PubMed] Related Publications
BACKGROUND: Dual-specificity phosphatase 6 (DUSP6) inactivates different target kinases to regulate cell proliferation and differentiation. Altered DUSP6 expressions or gene polymorphisms are associated with human cancer development including non-small cell lung cancer (NSCLC). DNA topoisomerase II alpha (TOP2A) regulates chromosome condensation and chromatid separation, and altered TOP2A expressions are associated with drug resistance development. This study assessed DUSP6 and TOP2A single nucleotide polymorphisms (SNPs) associated with NSCLC patient survival.
METHODS: This study included 152 surgically resected NSCLC patients and 277 chemoradiotherapy treated inoperable cases. DNA samples from each patient were genotyped for DUSP6 and TOP2A SNPs. Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard model were used to evaluate the association between these variants and NSCLC overall survival.
RESULTS: DUSP6 rs2279574 A/A genotype was associated with significantly poor inoperable NSCLC patient overall survival (A/A vs. C/C, adjusted HR = 1.549, 95% CI = 1.019-2.355). Stratification analysis against clinical stage, histology, weight loss, and ECOG performance status revealed that the DUSP6 rs2279574 A/A variant homozygous genotype is associated with a decrease in survival of stage IV NSCLC patients compared to those with the C/C genotype (log-rank, p = 0.003). No association was found among histology, weight loss, and ECOG performance status. Moreover, there was no association of TOP2A SNPs between clinicopathological and survival data.
CONCLUSIONS: Data obtained from the current study demonstrated that functional DUSP6 rs2279574 polymorphism was able to predict inoperable NSCLC patient survival after chemoradiotherapy.

Hou Y, Li Y, Gong F, et al.
A Preliminary Study on RCN3 Protein Expression in Non-small Cell Lung Cancer.
Clin Lab. 2016; 62(3):293-300 [PubMed] Related Publications
BACKGROUND: Reticulocalbin 3 (RCN3), a member of CREC (Cab45/reticulocalbin/ ERC-45/calumenin) family protein, is located in the secretory pathway of endoplasmic reticulum (ER) of living cells. Disruption of RCN3 leads to failure of lung function in the mouse model. Although ER stress has been associated with the development of a variety of tumors, the role of RCN3 in development of non-small cell lung cancer (NSCLC) in human is unknown at present.
METHODS: In this study a total of 41 paired NSCLC specimens (cancer group) and the adjacent normal tissues (control group) were obtained from patients undergoing lung lobectomy or pneumonectomy surgeries in Beijing Shijitan Hospital, Capital Medical University. The RCN3 mRNA and protein level in each clinical sample was determined using quantitative real time-PCR and immunoblotting, respectively. Immunohistochemistry analysis was utilized to compare the protein expressional patterns of RCN3 between the two clinical sample groups.
RESULTS: Immunoblotting showed that levels of RCN3 protein in the NSCLC tissues were significantly lower than those in the control group (p < 0.001), suggesting ER stress is closely associated with the cancer cells. Accordingly, the ER stress protein GRP78 (glucose-regulated protein 78, also known as BIP) was remarkably upregulated in the cancer group (p < 0.05). Within the cancer group, a significant difference in RCN3 protein expression was observed in squamous cell carcinoma versus adenocarcinoma (p < 0.05). In the lung cancer group, however, RCN3 protein levels were not correlated with the age and the gender. In addition, RCN3 mRNA levels showed no significant difference between the cancer and the control groups, suggesting that the differential regulation of RCN3 is likely at post-transcription stage in NSCLC.
CONCLUSIONS: Our study showed that RCN3 protein level was significantly down regulated in NSCLC, suggesting a potential correlation between RCN3 protein depletion and development of NSCLC. Although the exact cause-effect relationship between RCN3 and NSCLC needs to be further investigated, the study helps to shed additional lights on the molecular regulation of the lung cancer.

Koledin M, Koledin B, Ilincić D, Koledin S
A case of endobronchial leiomyoma treated by sleeve resection of the right upper lobe bronchus.
Vojnosanit Pregl. 2016; 73(2):208-10 [PubMed] Related Publications
INTRODUCTION: Bronchial leiomyoma is extremely rare. Most reported have been resected by either lobectomy or pneumonectomy. We presented a case treated by sleeve bronchoplasty without pulmonary resection.
CASE REPORT: The presented case, 39-year-old male, had been admitted to our hospital complaining of hemoptysis. Chest X-ray showed no abnormality in either lung field, but computed tomography scan found the tumor in the upper right bronchus. The diagnosis was made by histological and immunohistochemical examination of the specimens obtained during bronchoscopy.
CONCLUSION: The presented patient was treated by thoracotomy and sleeve resection of the right upper lobe bronchus with the removal of all the tumor.

Stojiljkovic D, Santrac N, Goran M, et al.
Factors related to local recurrence of non small cell lung cancer and its operability.
J BUON. 2016 Jan-Feb; 21(1):221-6 [PubMed] Related Publications
PURPOSE: To analyze the correlation of primary tumor (PT) pathological characteristics (size, stage, type and grade) and the extent of initial surgical treatment of non small cell lung cancer (NSCLC) with the incidence and time to local recurrence (LR) and disease-free survival (DFS), as well as to determine in what way these parameters and LR localizations affect the possibility for surgical retreatment.
METHODS: The research was conducted on 114 patients with NSCLC and LR that had initial surgery in two reference institutes in Serbia from January 2002 to December 2010. PT size and disease stage were defined according to the revised 2004 WHO classification. PTs were grouped by size into 3 categories. Due to great diversity, surgical procedures were sorted into 6 operation types. Standard statistical methods and tests were used for data analysis.
RESULTS: Statistical analyses showed significant difference in DFS and LR reoperability that were related to PT size, disease stage and the extent of initial surgery. LR localization on the chest wall was favorable for secondary surgery due to LR.
CONCLUSIONS: Squamous cell lung carcinoma relapses locally more frequently than other lung tumor types, and the commonest LR site is the chest wall. This localization provides high possibility for surgical retreatment. Adequate staging, proper indications for surgical treatment and quality surgery provide longer DFS in patients with NSCLC. All these suggest that the surgeon may be considered as the most significant factor of prognosis.

Gao YQ, Liu M, Zhang H
Expression profiles of SMAD1 protein in lung cancer tissues and normal tissues and its effect on lung cancer incidence.
J Biol Regul Homeost Agents. 2016 Jan-Mar; 30(1):165-71 [PubMed] Related Publications
The aim of this study is to detect the expression profiles of SMAD1 protein in lung cancer tissues and normal tissues to investigate its effect on the incidence of lung cancer. The expression profiles of SMAD1 protein in 60 cases of lung cancer tissues (lung cancer group), 25 cases of normal alveolus tissues (alveolus control group) and 29 cases of normal bronchial tissues (bronchial control group) were detected by adopting immunohistochemical analyses, and their relationships with clinicopathologic data were analyzed. The expression of SMAD1 protein in the lung cancer group and the lung squamous cell carcinoma group was significantly lower than that in the alveolus control group and the bronchial control group (P < 0.01). The expression of SMAD1 protein in the lung adenocarcinoma group was significantly lower than that in the alveolus control group and the bronchial control group (P < 0.01); The expression SMAD1 protein showed a significant correlation with lung cancer differentiation and lymphatic metastasis (P < 0.05), but not with genders, ages, tumor sizes and histological types of lung cancer patients (P>0.05).

Yan WX, Jia XJ, Chen YB, et al.
Primary small cell carcinoma of the vagina with pulmonary metastasis: a case report.
Eur J Gynaecol Oncol. 2016; 37(1):129-32 [PubMed] Related Publications
Primary small cell carcinoma of the vagina is extremely rare; no standard treatment has been established despite it being highly aggressive. Here, the authors report on a 43-year-old patient who had a mass on the clitoris and no uterine or bilateral adnexal involvement. Vaginal wall biopsy revealed malignant small cell carcinoma. The carcinoma was composed of epithelial cells with round, hyperchromatic nuclei containing few distinct nucleoli, and scanty cytoplasm. Chest computerized axial tomography and pathological bronchoscopy revealed bilateral pulmonary metastases. She received radiotherapy combined with six cycles of chemotherapy (paclitaxel plus cisplatin), and achieved complete response, with complete suppression of the mass and lung metastases. There was no sign of tumor recurrence or distant metastases after 21 months of follow-up.

Hong CM, Ahn BC
Can calcified pulmonary metastases detected by (18)F-FDG PET/CT suggest the primary tumor?
Hell J Nucl Med. 2016 Jan-Apr; 19(1):10-2 [PubMed] Related Publications
Many calcified nodules are encountered on the (18)F-FDG PET/CT scan and even though most of them are benign, the possibility of calcified pulmonary metastases (CPM) should be considered. The CT portion can often differentiate benign diseases due to their morphology. Measuring SUVmax is very important. Understanding the mechanism of calcification in malignant metastatic pulmonary lesions may be useful to suggest their origin.

Sawheny E, Khawar MU, Ahmad S, Jones K
Metastatic Lung Carcinoma Involving the Maxillary Gingiva.
J Okla State Med Assoc. 2016; 109(1):15-6 [PubMed] Related Publications
Metastatic spread of malignant tumors to the oral soft tissue is rare and account for 0.1% of all oral malignancies. Metastatic spread to the oral soft tissue can present as dental infections, which in turn can create a diagnostic challenge. Metastasis to the oral soft tissue from lung cancer is a rare situation. Here we describe a 52 year-old male patient treated initially with antibiotics for presumed oral abscess, who later was found to have metastatic lung cancer involving the maxillary gingiva.

Schaal JC, Lightfoot AF, Black KZ, et al.
Community-Guided Focus Group Analysis to Examine Cancer Disparities.
Prog Community Health Partnersh. 2016; 10(1):159-67 [PubMed] Article available free on PMC after 01/01/2017 Related Publications
BACKGROUND: Accountability for Cancer Care through Undoing Racism™ and Equity (ACCURE) is a systems-change intervention addressing disparities in treatment initiation and completion and outcomes for early stage Black and White breast and lung cancer patients. Using a community-based participatory research (CBPR) approach, ACCURE is guided by a diverse partnership involving academic researchers, a nonprofit community-based organization, its affiliated broader based community coalition, and providers and staff from two cancer centers.
OBJECTIVES: This paper describes the collaborative process our partnership used to conduct focus groups and to code and analyze the data to inform two components of the ACCURE intervention: 1) a "power analysis" of the cancer care system and 2) the development of the intervention's training component, Healthcare Equity Education and Training (HEET), for cancer center providers and staff.
METHODS: Using active involvement of community and academic partners at every stage in the process, we engaged Black and White breast and lung cancer survivors at two partner cancer centers in eight focus group discussions organized by race and cancer type. Participants were asked to describe "pressure point encounters" or critical incidents during their journey through the cancer system that facilitated or hindered their willingness to continue treatment. Community and academic members collaborated to plan and develop materials, conduct focus groups, and code and analyze data.
CONCLUSIONS: A collaborative qualitative data analysis process strengthened the capacity of our community-medical-academic partnership, enriched our research moving forward, and enhanced the transparency and accountability of our research approach.

Cekerevac I, Petrović M, Novković L, et al.
ECTOPIC ACTH SECRETION WITH CONCOMITANT HYPERAMYLASEMIA IN A PATIENT WITH SMALL CELL LUNG CARCINOMA: CASE REPORT.
Acta Clin Croat. 2015; 54(4):536-40 [PubMed] Related Publications
Histologically confirmed small cell lung cancer associated with Cushing's syndrome and elevated amylase is rarely described in the literature. We present a case of a 63-year-old patient admitted to cardiology department due to shortness of breath, exhaustion, palpitations and nausea. Elevated values of troponin and electrocardiography suggested that he could have acute coronary syndrome. According to the radiologist's opinion, plane lung radiography was normal. Elevated level of amylase was found in both serum (3802 U/L, normal range 28-100) and urine (12012 U/L, normal range 0-450 U/L), as well as elevated sodium (156 mmol/L, normal range 137-147 mmol/L), hyperglycemia (12 mmol/L, normal range 3.8-6.1 mmol/L) and lowered serum potassium (1.7 mmol/L, normal range 3.5-5.3 mmol/L). Computerized tomography (CT) of the abdomen revealed a tumor of the left adrenal gland and enlargement of the right adrenal gland with normal structure of the pancreas. During hospitalization, the patient had blood while coughing and CT scan of the lungs showed a tumor 48x38x51 mm in size localized in the laterobasal segment of the left lung with mediastinal lymphadenopathy. He also had bilateral pleural effusions with signs of pulmonary embolism, which explained elevated troponin values. Biopsy confirmed microcellular lung carcinoma and tumor cells were diffusely positive for TTF-1 and focally for CK7, expressing markers of neuroendocrine differentiation (chromogranin +++, synaptophysin +++, NSE ++). Since neuroendocrine tumor was confirmed and the patient had low potassium and high glucose, hypercortisolism was suspected. High morning cortisol (1784 mmol/L, normal range 171-536) and unsuppressed ACTH (214 pg/L, < 60), as well as a high level of chromogranin (1339 µg/L, < 65) were determined. During hospital stay, the patient developed heart and respiratory failure and died in the second week of hospitalization.

Liu XZ, Zhang LT, Tong WQ, et al.
Research Advances in Molecular Mechanisms of the Invasion and Metastasis of Lung Cancer.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2016; 38(1):108-12 [PubMed] Related Publications
The basic way of invasion and metastasis of lung cancer is that the tumor cells shed in the extracellular matrix, invade the basement membrane and the surrounding tissue, infiltrate into blood flow, and then survive and transport via the blood flow. After having been extravasated, migrated and arrested in the distant site, they finally form a metastatic lesion. Some basic mechanisms are required in these steps, such as tumor stem cells, diffusion and activity of tumor cells, escaping from apoptosis, angiogenesis and lymphangiogenesis, infiltration into blood flow, circulation and exudation, and distant metastasis proliferation. A better understanding of the mechanisms of the invasion and metastasis of lung cancer will facilitate the prevention and treatment of lung cancer.

Toshiyuki N, Kimura T, Suzumura T, et al.
The Macroscopic Appearance of Computed Tomography-guided Needle Biopsy Specimens Correlates with Tumor Metastasis in Non-small Cell Lung Cancer.
Osaka City Med J. 2015; 61(2):105-12 [PubMed] Related Publications
BACKGROUND: Computed tomography (CT)-guided needle biopsy is a well-established and dependable procedure for the diagnosis of pulmonary lesions. Some tissue biopsy samples have loose cohesion and disintegrate into tiny pieces before formalin fixation. The purpose of this study was to assess the association between the fresh macroscopic appearance of samples obtained using CT-guided needle biopsy and the clinicopathological features of non-small cell lung cancer (NSCLC).
METHODS: A total of 111 patients who underwent CT-guided lung needle biopsy at Osaka City University Hospital between May 2009 and May 2013 were enrolled. Macroscopic appearance was categorized as either loose or tight cohesion. Samples were evaluated using Azan staining to detect collagen fibers. The staining intensity was multiplied by the percentage of positive cells, and the specimen was categorized as having either low (<100) or high expression ( ≥100). Univariate and multivariate logistic regression models were used to evaluate significant covariates for tumor metastasis.
RESULTS: In the cohort of 111 patients, the diagnostic rates in loose and tight cohesions were 82.6% and 87.5%, respectively (p=0.509). In 60 patients diagnosed with NSCLC, Azan staining of collagen fibers was positive in 93.5% of the samples with tight cohesion and 28.6% of the samples with loose cohesion (p<0.001). In the multivariate logistic regression models, distant metastasis was significantly associated with loose cohesion (p=0.026).
CONCLUSIONS: These results suggest that the macroscopic appearance of CT-guided biopsy samples correlates with tumor metastasis in NSCLC.

Pedersen JH, Saghir Z, Wille MM, et al.
Ground-Glass Opacity Lung Nodules in the Era of Lung Cancer CT Screening: Radiology, Pathology, and Clinical Management.
Oncology (Williston Park). 2016; 30(3):266-74 [PubMed] Related Publications
The advent of computed tomography screening for lung cancer will increase the incidence of ground-glass opacity (GGO) nodules detected and referred for diagnostic evaluation and management. GGO nodules remain a diagnostic challenge; therefore, a more systematic approach is necessary to ensure correct diagnosis and optimal management. Here we present the latest advances in the radiologic imaging and pathology of GGO nodules, demonstrating that radiologic features are increasingly predictive of the pathology of GGO nodules. We review the current guidelines from the Fleischner Society, the National Comprehensive Cancer Network, and the British Thoracic Society. In addition, we discuss the management and follow-up of GGO nodules in the light of experience from screening trials. Minimally invasive tissue biopsies and the marking of GGO nodules for surgery are new and rapidly developing fields that will yield improvements in both diagnosis and treatment. The standard-of-care surgical treatment of early lung cancer is still minimally invasive lobectomy with systematic lymph node dissection. However, recent research has shown that some GGO lesions may be treated with sublobar resections; these findings may expand the surgical treatment options available in the future.

Headley MB, Bins A, Nip A, et al.
Visualization of immediate immune responses to pioneer metastatic cells in the lung.
Nature. 2016; 531(7595):513-7 [PubMed] Article available free on PMC after 01/01/2017 Related Publications
Lung metastasis is the lethal determinant in many cancers and a number of lines of evidence point to monocytes and macrophages having key roles in its development. Yet little is known about the immediate fate of incoming tumour cells as they colonize this tissue, and even less known about how they make first contact with the immune system. Primary tumours liberate circulating tumour cells (CTCs) into the blood and we have developed a stable intravital two-photon lung imaging model in mice for direct observation of the arrival of CTCs and subsequent host interaction. Here we show dynamic generation of tumour microparticles in shear flow in the capillaries within minutes of CTC entry. Rather than dispersing under flow, many of these microparticles remain attached to the lung vasculature or independently migrate along the inner walls of vessels. Using fluorescent lineage reporters and flow cytometry, we observed 'waves' of distinct myeloid cell subsets that load differentially and sequentially with this CTC-derived material. Many of these tumour-ingesting myeloid cells collectively accumulated in the lung interstitium along with the successful metastatic cells and, as previously understood, promote the development of successful metastases from surviving tumour cells. Although the numbers of these cells rise globally in the lung with metastatic exposure and ingesting myeloid cells undergo phenotypic changes associated with microparticle ingestion, a consistently sparse population of resident conventional dendritic cells, among the last cells to interact with CTCs, confer anti-metastatic protection. This work reveals that CTC fragmentation generates immune-interacting intermediates, and defines a competitive relationship between phagocyte populations for tumour loading during metastatic cell seeding.

Fehrenbacher L, Spira A, Ballinger M, et al.
Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial.
Lancet. 2016; 387(10030):1837-46 [PubMed] Related Publications
BACKGROUND: Outcomes are poor for patients with previously treated, advanced or metastatic non-small-cell lung cancer (NSCLC). The anti-programmed death ligand 1 (PD-L1) antibody atezolizumab is clinically active against cancer, including NSCLC, especially cancers expressing PD-L1 on tumour cells, tumour-infiltrating immune cells, or both. We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC, analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population.
METHODS: In this open-label, phase 2 randomised controlled trial, patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practices across 13 countries in Europe and North America. Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), and adequate haematological and end-organ function. Patients were stratified by PD-L1 tumour-infiltrating immune cell status, histology, and previous lines of therapy, and randomly assigned (1:1) by permuted block randomisation (with a block size of four) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m(2) once every 3 weeks. Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells (as percentage of PD-L1-expressing tumour cells TC3≥50%, TC2≥5% and <50%, TC1≥1% and <5%, and TC0<1%) and tumour-infiltrating immune cells (as percentage of tumour area: IC3≥10%, IC2≥5% and <10%, IC1≥1% and <5%, and IC0<1%). The primary endpoint was overall survival in the intention-to-treat population and PD-L1 subgroups at 173 deaths. Biomarkers were assessed in an exploratory analysis. We assessed safety in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01903993.
FINDINGS: Patients were enrolled between Aug 5, 2013, and March 31, 2014. 144 patients were randomly allocated to the atezolizumab group, and 143 to the docetaxel group. 142 patients received at least one dose of atezolizumab and 135 received docetaxel. Overall survival in the intention-to-treat population was 12·6 months (95% CI 9·7-16·4) for atezolizumab versus 9·7 months (8·6-12·0) for docetaxel (hazard ratio [HR] 0·73 [95% CI 0·53-0·99]; p=0·04). Increasing improvement in overall survival was associated with increasing PD-L1 expression (TC3 or IC3 HR 0·49 [0·22-1·07; p=0·068], TC2/3 or IC2/3 HR 0·54 [0·33-0·89; p=0·014], TC1/2/3 or IC1/2/3 HR 0·59 [0·40-0·85; p=0·005], TC0 and IC0 HR 1·04 [0·62-1·75; p=0·871]). In our exploratory analysis, patients with pre-existing immunity, defined by high T-effector-interferon-γ-associated gene expression, had improved overall survival with atezolizumab. 11 (8%) patients in the atezolizumab group discontinued because of adverse events versus 30 (22%) patients in the docetaxel group. 16 (11%) patients in the atezolizumab group versus 52 (39%) patients in the docetaxel group had treatment-related grade 3-4 adverse events, and one (<1%) patient in the atezolizumab group versus three (2%) patients in the docetaxel group died from a treatment-related adverse event.
INTERPRETATION: Atezolizumab significantly improved survival compared with docetaxel in patients with previously treated NSCLC. Improvement correlated with PD-L1 immunohistochemistry expression on tumour cells and tumour-infiltrating immune cells, suggesting that PD-L1 expression is predictive for atezolizumab benefit. Atezolizumab was well tolerated, with a safety profile distinct from chemotherapy.
FUNDING: F Hoffmann-La Roche/Genentech Inc.

Xu XL, Song W, Sui X, et al.
Computed Tomographic and Pathological Features of Primary Pulmonary Sarcomatoid Carcinoma.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2016; 38(1):93-8 [PubMed] Related Publications
OBJECTIVE: To investigate the computed tomographic (CT) and pathological features of primary pulmonary sarcomatoid carcinoma (PSC).
METHODS: The clinical data and CT images of 20 patients with pathologically confirmed PSC were retrospectively analyzed.
RESULTS: Solitary pulmonary mass was identified in 18 patients and multiple pulmonary masses in 2 patients, amounting to 22 masses. There were 17 peripheral masses and 5 central masses, including 11 masses larger than 5 cm. The smooth margin was identified in 9 masses, deep lobulation and/or spinous protuberance in 11 masses, and ill-defined margin in 2 masses. Pleural indentation was identified in 2 masses and pleural thickening with wide basement was identified in 14 masses. On plain CT, cavity was observed in 5 masses, hypo-density in 7 masses, and homogeneous density in 10 masses. On contrast-enhanced CT scanning, irregular ring/patchy enhancement were shown in 15 masses and slightly homogenous enhancement in 2 masses. Of all patients, 6 patients had unilateral or bilateral hilar and/or mediastinal lymphadenopathy. There were 16 pleomorphic carcinomas and 4 spindle cell carcinomas. Immunohistochemically, anti-pan cytokeratin antibody was positive in 13 patients, cytokeratin was positive in 8 patients, Vimentin was positive in 15 patients, epithelial membrane antigen was positive in 1 patient, and thyroid transcription factor-1 was positive in 8 patients.
CONCLUSION: PSC has some specific CT features; however, the final confirmation of PSC still depends on pathological and immunohistochemical examinations.

Hawrysz I, Krusińska B, Słowińska MA, et al.
Nutritional knowledge, diet quality and breast or lung cancer risk: a case-control study of adults from Warmia and Mazury region in Poland.
Rocz Panstw Zakl Hig. 2016; 67(1):9-15 [PubMed] Related Publications
BACKGROUND: Knowledge on proper nutrition favours the creation of pro-healthy nutritional behaviours of people. Studies related to the nutritional knowledge of adults, diet quality and incidence of breast or lung cancers are limited.
OBJECTIVE: Analysis of the relationship between the level of nutritional knowledge, diet quality and risk of breast cancer in women or lung cancer in men from the Warmia and Mazury region in Poland.
MATERIAL AND METHODS: The study was carried out in 202 subjects aged 23-80 years, including 107 women (17 cases of breast cancer) and 95 men (54 cases of lung cancer) from the Warmia and Mazury region in Poland. Nutritional knowledge was evaluated with the Questionnaire of Eating Behaviours (QEB), including 25 statements. Based on the frequency of the consumption of 16 food items, two diet quality indices were created: the pro-Healthy-Diet-Index-8 (pHDI-8) and the non-Healthy-Diet-Index-8 (nHDI-8). The values of pHDI-8 and nHDI-8 were calculated on the basis of the sum of the daily frequency of consumption of the selected food items and expressed as times/day. The Odds Ratio (OR) of both breast cancer or lung cancer in relation to the level of nutritional knowledge was calculated based on a logistic regression analysis.
RESULTS: The incidence of breast or lung cancer in the bottom, middle and upper tertile of nutritional knowledge was 57.6%, 32.6% and 15.8%, respectively. As nutritional knowledge grew in the subsequent tertiles, pHDI-8 was on the increase (2.63 vs. 3.78 vs. 4.22 times/day) and n-HDI-8 was on the decrease (1.32 vs. 1.21 vs. 0.94 times/day). In the upper tertile of nutritional knowledge, the Odds Ratio for the incidence of breast or lung cancers varied from 0.06 (95% CI: 0.02; 0.17; p<0.05, with adjustment for cancer type and age) to 0.17 (95% CI: 0.04; 0.69; p<0.05, with adjustment for age and sex) when compared to the bottom tertile (OR=1.00). In the middle tertile of nutritional knowledge, the Odds Ratio of both cancers varied from 0.27 (95% CI: 0.12; 0.62, p<0.05, with adjustment for cancer type and age) to 0.35 (95% CI: 0.18; 0.71, p<0.05, variables without adjustment) when compared to the bottom tertile.
CONCLUSIONS: A higher level of nutritional knowledge was associated with the higher quality of a pro-healthy diet and lower risk of breast cancer in women or lung cancer in men. In contrast, a lower level of nutritional knowledge was associated with a lower diet quality and a higher risk of both types of cancers.

Zhao Z, Liao H, Ju Y
Effect of compound Kushen injection on T-cell subgroups and natural killer cells in patients with locally advanced non-small-cell lung cancer treated with concomitant radiochemotherapy.
J Tradit Chin Med. 2016; 36(1):14-8 [PubMed] Related Publications
OBJECTIVE: To observe effect of compound Kushen injection on T-cell subgroups and NK cells in patients with locally advanced non-small-cell lung cancer (NSCLC) treated with concomitant radiochemotherapy.
METHODS: We randomly divided 60 patients with locally advanced NSCLC who were treated at our hospital between May 2011 and May 2013 into a treatment group and a control group by drawing. The treatment group (n = 30) received concomitant radiochemotherapy plus compound Keshen injection, and the control group (n = 30) received only radiochemotherapy.
RESULTS: After treatment, levels of CD3+, CD4+, CD4+/CD8+ and CD16+/CD56+ cells had significantly increased, and CD8+ cells had significantly decreased, in the treatment group compared with both their pretreatment levels and with levels in the control group. In the control group, post-treatment levels of CD3 +, CD4 +, CD4 +/CD8 + and CD16+/CD56+ cells were not significantly changed from pretreatment levels. The two groups did not significantly differ in their rates of toxicity reactions (P> 0.05).
CONCLUSION: Compound Kushen injections can increase immunologic function in patients with locally advanced non-small cell lung cancer who receive concomitant radiochemotherapy.

Czyżykowski R, Połowinczak-Przybyłek J, Potemski P
Nicotine-induced resistance of non-small cell lung cancer to treatment--possible mechanisms.
Postepy Hig Med Dosw (Online). 2016; 70:186-93 [PubMed] Related Publications
Cigarette smoking is the leading risk factor of lung cancer. Data from several clinical studies suggest that continuation of smoking during therapy of tobacco-related cancers is associated with lower response rates to chemotherapy and/or radiotherapy, and even with decreased survival. Although nicotine--an addictive component of tobacco--is not a carcinogen, it may influence cancer development and progression or effectiveness of anti-cancer therapy. Several in vitro and in vivo trials have evaluated the influence of nicotine on lung cancer cells. The best known mechanisms by which nicotine impacts cancer biology involve suppression of apoptosis induced by certain drugs or radiation, promotion of proliferation, angiogenesis, invasion and migration of cancer cells. This effect is mainly mediated by membranous nicotinic acetylcholine receptors whose stimulation leads to sustained activation of such intracellular pathways as PI3K/Akt/mTOR, RAS/RAF/MEK/ERK and JAK/STAT, induction of NF-κB activity, enhanced transcription of mitogenic promoters, inhibition of the mitochondrial death pathway or stimulation of pro-angiogenic factors. We herein summarize the mechanisms underlying nicotine's influence on biology of lung cancer cells and the effectiveness of anti-cancer therapy.

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